Immunotherapy for Cancer

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Personalized Immunotherapy

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Around the world, infection is one of the most important causes of cancer and chronic inflammatory disorders. A certain percentage of malignancies or chronic diseases can be attributed to infectious agents. RCT believes that there is a higher percentage than what is currently recognized by the scientific community due to the results observed by RCT’s doctors and scientists. At RCT, the field of cancer vaccines is currently in an active state of clinical investigations, as many forms of solid-state tumors continue to affect a large portion of the population and new infectious agents emerge as a root cause of chronic illnesses.

As many researchers continue to hunt for a root cause, a robust innovative treatment may have shined a light on an internal weakness of the human body which is allowing cancer to proliferate.

The human immune system does fight cancer. In reality, it is not pathogens that do the good work. It is the way our bodies respond to pathogens.

RCT’s cancer immunotherapy is an innovative approach that stimulates the human innate immune system and shifts it into higher gear. That ultimately improves the crucial biological machinery in the adaptive immune system.

Healthy immune system produces specific antibodies, proteins with complex 3-dimensional structure capable of binding to the surfaces of foreign bodies (bacteria, viruses or parasites) in a key-lock fashion. In this complex process our body tags the cells, and activates a cascade of processes for cell destruction.

Human Microbiome and Cancer

Extensive research in the area of immunotherapy has revealed numerous pathogens as causative agents of cancer and other chronic conditions. H. pylori (gastric carcinoma), human papilloma (cervical carcinoma), human polyomaviruses (mesotheliomas, brain tumors), Epstein-Barr virus (B-cell lymphoproliferative diseases and nasopharyngeal carcinoma, hepatitis B and hepatitis C viruses (hepatocellular carcinoma), human T-cell leukemia Virus-1 are just a few examples.

IMG1
Helicobacter pylori bacteria. Colored transmission electron micrograph (TEM) of a section of the surface of a human stomach infected with Helicobacter pylori bacteria (pink). Formerly known as Campylobacter pyloridis, these are spiral-shaped Gram-negative bacteria. Colonies of H. pylori are found in the mucus lining of the stomach. They cause gastritis, and are also the most common cause of stomach ulcers. H. pylori may also be a cause or co-factor for gastric cancer, as its presence increases the risk of developing stomach tumours. Magnification x38,500.
hpv-web
Papilloma Virus (HPV) Electron micrograph of a negatively stained human papilloma virus (HBV) which occurs in human warts. Warts on the hands and feet have never been known to progress to cancer. However, after many years cervical warts can become cancerous.

It has been scientifically proven that some microorganisms have the ability to get into stealth mode and remain unrecognized, undetected and stay dormant until the host’s immune system becomes suppressed and compromised. At that moment those opportunistic pathogens seize the opportunity to attack. The elusive microorganism can move out of its typical environment and into other parts of the body by hitching the ride and begin causing other diseases. This group of pathogens has been discovered in the urogenital tract of patients suffering from inflammatory pelvic disease, urethritis and other urinary tract diseases; in the heart tissues and fluid patients suffering from pericarditis, tachycardia, hemolytic anemia and other coronary diseases; in the cerebrospinal fluid of patients with meningitis and encephalitis, seizure, ALS, Alzheimer’s and other central nervous system infections; in the bone marrow of children with leukemia. Today, over 100 documented species of the organism have been recorded to cause various diseases in humans, animals, and plants.

IMG3
Bacterial pathogen (smaller features in the image) is associated with nonpulmonary manifestations, such as blood, skin, joint, central nervous system, liver, pancreas, and cardiovascular syndromes and disorders, often linked to cancer.

In our state-of-the art research facilities we are capable of discovering new pathogens, both known and unidentified, yet to be implicated in human chronic diseases.

Our comprehensive immunotherapy regimen, including the vaccine, is helping the immune system to recognize pathogens that might be contributing to chronic degenerative diseases such as cancer, lupus, scleroderma, lime disease, MRSA and many other conditions related to the human immune system.

Comprehensive and robust immunotherapy regimens often have fewer side effects than existing drugs, including potential for creating resistance in microbial diseases.

  • Adenocarcinoma
  • Bone cancer
  • Breast Cancer
  • Colon Cancer
  • Kidney Cancer
  • Liver Cancer
  • Lung Cancer
  • Lymphoma
  • Melanoma
  • Ovarian Cancer
  • Osteosarcoma
  • Pancreatic Cancer
  • Prostate Cancer
  • Rhabdomyosarcoma
  • Sarcoma
  • Squamous Cell Cancer
  • Stomach Cancer
  • Teratoma
  • Testicular Cancer
  • Thyroid Cancer
  • Uterine Cancer

What Makes RCT Different?

Tailored Targeting Multiple Antigens Simultaneously

Most cancer vaccines target a single pathogen or tumor specific antigen and may be less effective. Tumors and human microbiome are highly heterogeneous and antigen expression differs markedly between tumors (even in the same patient). To make vaccine more effective, our vaccines are targeted against a broad range of pathogens and antigens but yet highly specific for each patient.

Implementation of a personalized approach to enhance treatment efficacy and reduce side-effects has resulted in a 70-75% complete remission in patients diagnosed with stage III and stage IV cancers. We believe that by introducing latest scientific and technological advancements our success will just get higher.

How Does it Work?

Personalized immunotherapeutic vaccines are designed to teach the immune system to attack and destroy microbial pathogens. Microorganisms express various proteins (antigens) on their surface. It is well known that they can modulate their surface protein modulation, depending on the environmental conditions. Antigens are protruding out of bacterial cell wall. It is well known that, depending on environmental conditions, bacteria modulate their surface protein organization. Certain surface-exposed antigens interact and constitute protein complexes, unique to each patient.

One of the greatest advantages of immunotherapeutic vaccines is the fact that they are made only from patients own bacteria, ensuring unprecedented specificity. When isolated and grown artificially in large quantities, inactivated and introduced back into the patient, immune system is taught to recognize bacterial surface antigens, an immune system is activated against the pathogen invader.

Vaccination with personalized vaccines, which are derived from patient’s microbiome, has the benefit of conditioning the immune system to activate an immune response against patient’s unique bacterial antigens, as well as target multiple unknown antigens simultaneously. Vaccine boosts a patient’s pre-existing immune response and is capable of inducing an immune response against new bacterial antigens in patients lacking spontaneous immunity.

Use of Proprietary Peptide Adjuvants

An effective immunotherapeutic vaccine for cancer must overcome several challenges. The vaccines seek to target a specific tumor antigen and distinct from self-proteins. Antigens and other substances are often not strong enough inducers of the immune response to make effective cancer treatment vaccines. Incorporating a proprietary peptide adjuvant induces cellular and hormonal responses. The peptide binds with the surface of the tumor cells and inhibits its growth by inducing anti-angiogenesis. As a result, circulation to the tumor tissue is inhibited, thus causing the tumor to shrink. Moreover, the peptide activates antigen-presenting cells and enhances and stimulates the immune response. An effective vaccine also provides immune system long-term memory and prevents tumor recurrence. Some scientists believe that for total tumor elimination, both the innate and adaptive immune system should be activated.

Combining and Supplementing Cancer Vaccine with Other Types of Cancer Therapy

In many of the clinical trials of cancer treatment vaccines that are now under way, vaccines are being given with other forms of cancer therapy. Therapies that have been combined with the cancer vaccines include surgery, chemotherapy, radiation therapy and some forms of targeted therapies that are intended to boost immune system.

Several studies have suggested that cancer treatment vaccines may be most effective when given in combination with other forms of cancer therapy. In addition, in some clinical trials, cancer treatment vaccines have appeared to increase the effectiveness.

Vaccine Side Effects

Vaccines intended to prevent or treat cancer appear to have safety profiles comparable to those of traditional vaccines. However, the side effects can vary among vaccine formulations and from one person to another.

The most commonly reported side effect of vaccines is inflammation at the site of injection, including redness, mild pain, swelling, warming of the skin, itchiness, and occasionally a rash.

RCT’s Personalized Immunotherapy is Now Available!

growth-factor-iconRCT’s immunotherapy is a series of injectables, individually tailored for each patient. It includes 1-3 sets of treatments, with each set lasting 30 weeks. RCT’s doctors will be able to identify if the immunotherapy is working within the first 30-60 days of the first set.

The treatments are made from cultures of the cancer causing mycobacterium, which is isolated from each patient’s urine. These organisms are then grown to a specific level and killed. This compound is then made into an injectable at RCT’s lab. After administering the treatment, the patients body will begin to create antibodies to target and wipeout the microorganisms, which are at the root of cancer proliferation.

Testing Results

Detection and quantitation of specific nucleic acid sequences using polymerase chain reaction (PCR) is fundamental to a growing number of molecular diagnostic tests. The latest and most advanced among various PCR techniques is digital droplet PCR (ddPCR). This extremely powerful technique is capable of detecting a single copy of very specific sequences and it is the only technique that provides the absolute value (number), which is in direct correlation to the initial copy number in the sample. The ddPCR is used to study cancer markers and copy number variation, detect pathogens, analyze gene expression, detect rare mutations and quantify the bacterial or viral load. The technique is superior to all other quantitative techniques and has unprecedented sensitivity and reproducibility. Fast feedback and absolute quantitative analysis is a tool that enables closely following patient’s progression or regression throughout the course of treatment and adjusting the treatment to achieve best possible outcome.

During the treatment, patients can start or continue receiving supplementary treatments, such as antibiotics, nutritional supplements, digestive enzymes, bile salts, enemas, laxatives, or blood transfusions. For all patients, a strict vegetarian diet is required to participate.

RCT is Now Accepting New Patient Applications!


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References

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  1. Alexander, F.E. (1997). “Pneumonia associated with childhood acute lymphoblastic anemia? ” Cancer Causes Control 8(5): 803-811.

Acute lymphoblastic leukemia (ALL) in the childhood peak may be a rare response to delayed first exposure to one or more common infectious agent(s). Mycoplasma Pneumonia has the appropriate socioeconomic correlates and clinical symptoms and the hypothesis that delayed first exposure to it may contribute to ALL is considered. Counts of positive reports of M Pneumonia from disease surveillance data for England and Wales (United Kindom) for 1975-92 have been taken as proxies for community burden of infection. Variation by months of birth (cohort) and diagnosis (period) of incidence of ALL in children born and diagnosed 1975-92 are compared with predictions. When periods were classified by mean M Pneumonia count rate in the nine preceding months, standardized morbidity ratios (SMR) for the highest and lowest 20 percent were 108 and 89 (rate ratio [RR] = 1.2, 95 percent confidence interval [CI] = 1.1-1.4). SMRs for cohorts with highest and lowest predicted risk (i.e., lowest and highest M Pneumonia count rate around birth and during infancy) were 110 and 97 (RR = 1.1, CI = 1.0-1.3). The trend for period was most marked in the cohorts with low opportunity for exposure when young. This ecologic analysis provides preliminary support for the hypothesis.

  1. Cantwell, A. R. and D. W. Kelso (1980). “Autopsy findings of nonacid-fast bacteria in scleroderma.” Dermatologica 160(2): 90-99.

Microscopic tissue sections stained for bacteria were studied from autopsy material from a fatal case of scleroderma (progressive systemic sclerosis). Extra-and intracellular, variable-sized, pleomorphic but predominantly coccoid bacteria were observed in some organs such as in heart, lungs, adrenals, kidneys, pancreas, skin, and in the connective tissue. An attempt is made to correlate the ante-mortem skin culture material with the post-mortem histopathologic finding of bacteria. It is hypothesized that these microbes observed in tissue might represent in vivo, cell wall deficient L forms, which may be implicated in the pathogenesis of scleroderma.

  1. Chirino-Trejo, M., et al. (2003). “Antibiotic sensitivity and biochemical characterization of Fusobacterium spp. and Arcanobacterium pyogenes isolated from farmed white-tailed deer (Odocoileus virginianus) with necrobacillosis.” J Zoo Wildl Med 34(3): 262-268.

Bacterial cultures from 32 living and dead farmed white-tailed deer (Odocoileus virginianus) with necrobacillosis yielded Fusobacterium necrophorum from nine individuals, F. varium from six individuals, and Arcanobacterium pyogenes from 16 individuals. The isolates were characterized biochemically using automated identification systems. Gram-stained smears suggested the presence of Fusobacterium spp. in eight cases from which organisms were not cultured. Minimum inhibitory concentration determinations in 23 strains of gram-negative anaerobic bacteria detected resistance to enrofloxacin and clindamycin. Enrofloxacin resistance was detected in A. pyogenes isolates, and although biochemical profiling indicated that the deer strains of A. pyogenes could be grouped, it is uncertain whether these biochemical characteristics correlate with antigenic or virulence factors. Deer-specific or autogenous vaccines may provide a useful alternative to generic vaccines.

  1. Chukiatsiri, K., et al. (2009). “Efficacy of autogenous killed vaccine of Avibacterium paragallinarum.” Avian Dis 53(3): 382-386.

The efficacy of killed vaccine of Avibacterium paragallinarum with mineral oil adjuvant and aluminum hydroxide gel adjuvant was tested for antibody titers and protection. The autogenous vaccines at a concentration of 10(10) colony-forming units (CFU)/ml were administered to 5-wk-old male layers by subcutaneous injection in the neck twice at a 3-wk interval. Each chicken was challenged with 10(8) CFU/ml in 400 microl of an homologous isolate of A. paragallinarum serotype A, IR1, at 4 wk after the second vaccination via the nasal route. Sera were collected and the antibodies were tested by the hemagglutination inhibition test. The results revealed that the autogenous mineral oil adjuvant vaccine provided the antibody titer significantly faster than the other groups (P < 0.05). The average antibody titers of the group vaccinated with autogenous mineral oil adjuvant vaccine were higher than those of the group vaccinated with autogenous aluminum hydroxide gel adjuvant vaccine. The protective ability of vaccines was assessed by infraorbital sinus swab after 5 days postchallenge. The autogenous vaccines prepared with mineral oil adjuvant and aluminum hydroxide gel adjuvant protected all the chickens after challenge. No bacteria were isolated from the infraorbital sinuses of chickens in either autogenous vaccine group with either high or low antibody titers. The commercial vaccines prepared from mineral oil or aluminum hydroxide gel adjuvant revealed some protection. This is in contrast to the unvaccinated control group, in which facial edema and serous nasal discharge was found, and bacteria could be isolated from all chickens in the group.

  1. Chukiatsiri, K., et al. (2009). “Efficacy of autogenous killed vaccine of Avibacterium paragallinarum.” Avian Dis 53(3): 382-386.

The efficacy of killed vaccine of Avibacterium paragallinarum with mineral oil adjuvant and aluminum hydroxide gel adjuvant was tested for antibody titers and protection. The autogenous vaccines at a concentration of 10(10) colony-forming units (CFU)/ml were administered to 5-wk-old male layers by subcutaneous injection in the neck twice at a 3-wk interval. Each chicken was challenged with 10(8) CFU/ml in 400 microl of an homologous isolate of A. paragallinarum serotype A, IR1, at 4 wk after the second vaccination via the nasal route. Sera were collected and the antibodies were tested by the hemagglutination inhibition test. The results revealed that the autogenous mineral oil adjuvant vaccine provided the antibody titer significantly faster than the other groups (P < 0.05). The average antibody titers of the group vaccinated with autogenous mineral oil adjuvant vaccine were higher than those of the group vaccinated with autogenous aluminum hydroxide gel adjuvant vaccine. The protective ability of vaccines was assessed by infraorbital sinus swab after 5 days postchallenge. The autogenous vaccines prepared with mineral oil adjuvant and aluminum hydroxide gel adjuvant protected all the chickens after challenge. No bacteria were isolated from the infraorbital sinuses of chickens in either autogenous vaccine group with either high or low antibody titers. The commercial vaccines prepared from mineral oil or aluminum hydroxide gel adjuvant revealed some protection. This is in contrast to the unvaccinated control group, in which facial edema and serous nasal discharge was found, and bacteria could be isolated from all chickens in the group.

  1. Cunningham, T. J., et al. (1976). “Adjuvant immuno- and/or chemotherapy with neuraminidase-treated autogenous tumor vaccine and Bacillus Calmette-Guerin for head and neck cancers.” Ann N Y Acad Sci 277(00): 339-344.

Cancer immunotherapy trials were initially attempted in patients with metastatic disease who progressed on standard therapy. Failures were often attributed to the advance stage of the disease and to the inability to produce an effective antigenic vaccine. To date, one of the most successful animal models for immunotherapy programs has been that of Simmons and Rios, in which Vibrio cholera neurominidasc (VCN)-treated tumor cells were combined with Bacillus Calmette-Guerin (BCG). The addition of chemoimmunotherapy has been reported to be superior to chemotherapy alone. In an attempt to approach the animal model in which previous immunization prevents the growth of new tumor challenge and yet still employ this unproven method of cancer treatment, we chose patients with advanced carcinoma of the head and neck who primarily had regional disease and a poor prognosis. In these patients, surgery and/or radiation therapy are standard modes of treatment and are effective nitially eliminating macroscopic disease. This study was designed to examine some of the parameters necessary to effectively undertake a cooperative group adjuvant chemoimmunotherapy study in patients with head and neck cancer, in addition to gaining experience with VCN-treated autologous tumor vaccine.

  1. Dacbock et al. (2001) “Severe hemolytic anemia and excessive leukocytosis masking mycoplasma pneumonia.” Ann Heatol. 80(3): 180-182.

The formation of cold agglutinins is frequently observed during Mycoplasma pneumoniae infections. Nevertheless, severe hemolysis is exceptional. We report a case of life-threatening hemolytic anemia caused by M. pneumoniae. As the leucocyte count was excessively elevated, the differential diagnosis primarily comprised hematological malignancies. The presence of cold agglutinins indicated the correct diagnosis, which was confirmed by highly elevated levels of both IgG and IgM antibodies to M. pneumoniae and a chest X-ray suggestive of atypical pneumonia. The patient was treated with roxithromycin and showed a favorable recovery within ten days after admission. This case demonstrates that, even in patients with clinically mild pneumonia, M. pneumoniae may be the cause of severe anemia.

  1. Das, A. M. and V. L. Paranjape (1988). “Autogenous vaccine therapy in human cutaneous staphylococcosis.” Indian J Med Res 88: 404-408.
  1. Elias, E. G. and B. K. Sharma (2014). “Melanoma vaccines, revisited: a review, update.” G Ital Dermatol Venereol 149(6): 711-717.

Melanoma vaccines are usually administered after surgical resection of the tumor with the hope of eradicating the micrometastases, in high-risk patients. As we previously reported, most of the melanoma vaccines failed to show any major impact on the disease, except for the autologous whole cell vaccine. This can be explained by the heterogeneous nature of cutaneous melanoma that expresses various levels of melanoma antigens, peptides and has various genetic profiles among different patients. From an immunological point of view, it is illogic to eliminate the tumor and its specific antigens then apply allogenic type of therapy and expect a tumor response. Therefore, it is more logical is to utilize the tumor site as a source for the tumor-specific antigens. In the meantime, patients with in-transit metastases can give us an excellent opportunity to evaluate the local and systemic effects of intralesional (intratumoral) therapy, and various agents have been utilized with equivocal results. On the other hand, intralesional administration of 2 cytokines seemed to process the tumor antigens and activates thymic-derived lymphocytes (T cells). This can induce an antitumor immune response in vivo, i.e., autoimmunization (auto-vaccination), specific to each patient, and overcome tumor heterogeneity regardless to its antigenic or genetic profiles.

  1. Goulet, M et al (1995). “Isolation of Mycoplasma pneumoniae from the human urogenital tract.” J Clin Microbiol 33: 2823-2825.
  1. Graham, J. B. and R. Graham (1969). “Pseudomyxoma peritonei treated with autogenous vaccine.” Clin Obstet Gynecol 12(4): 955-957.
  1. Hallamaa, R. E., et al. (2005). “Macroscopical and histopathological changes in regressing primary and recurrent equine sarcoids during active specific bio-immunotherapy.” In Vivo 19(4): 761-767.

Healing sarcoids were followed in 18 horses which had taken part in previous clinical studies on a total of 29 horses suffering from either primary or recurrent sarcoids, treated with bio-immunotherapy. In the present study, attention was paid to changes observed in these fibroblastic skin tumours during their regression. The tumours were surgically debulked leaving the base in the skin. The horses were immunized according to bio-immunotherapy at 2- to 4-week intervals with an autogenous vaccine made from the excised part of the tumour until the base had visibly regressed. Healing was followed by inspections and serial biopsies from the base, studied under light microscope. Visibly normal epithelisation developed first at the margin of the base, progressing gradually to the centre. The mean rate of epithelisation was approximately equal to normal horse skin. Most of the histopathological features typical of equine sarcoid diminished significantly in the follow-up biopsies, when the first signs of visibly normal epithelisation were observed. The changes were more evident among the primary than the recurrent tumours. No leucocyte infiltration, lysis or apoptosis were found during the regression. Bio-immunotherapy seems to simulate a spontaneous healing process.

  1. Holinger, P. H., et al. (1968). “Studies of etiology of laryngeal papilloma and an autogenous laryngeal papilloma vaccine.” Acta Otolaryngol 65(1): 63-69.
  1. Kardos, G., et al. (2007). “DNA fingerprinting analysis of breakthrough outbreaks in vaccine-protected poultry stocks.” Clin Vaccine Immunol 14(12): 1649-1651.

We report recurrent outbreaks of Yersinia pseudotuberculosis conjunctivitis in ducks and of fowl cholera in geese, occurring in stocks previously vaccinated with inactivated autogenous vaccines. Enterobacterial repetitive intergenic consensus sequence-based PCR and pulsed-field gel electrophoresis indicated reinfection with a new Y. pseudotuberculosis strain and vaccine evasion by the same Pasteurella multocida strain.

  1. Kinnunen, R. E., et al. (1999). “Equine sarcoid tumour treated by autogenous tumour vaccine.” Anticancer Res 19(4C): 3367-3374.

Twenty-one horses with sarcoid tumours were treated by bio-immunotherapy using autogenous vaccines during 1991-1997. At operation the base of the tumour was left in the skin and autovaccines were made from extirpated tumour tissue by polymerization. The horses thus formed their own internal control group. One of 12 horses having a primary tumour, and four of 9 horses suffering recurrent tumours, prior to bio-immunotherapy, developed single recurrences. Four of these five horses suffering recurrence were treated anew, leading to remission. Disease-free intervals were longer for primary (P = 0.0005) and recurrent sarcoids (P = 0.0156) than for conventional surgery alone. Mitochondrial events seem to effect the healing.

  1. Kumar, R., et al. (1997). “Hydropericardium syndrome (HPS) in India: a preliminary study on the causative agent and control of the disease by inactivated autogenous vaccine.” Trop Anim Health Prod 29(3): 158-164.

Hydropericardium syndrome (HPS) in broiler birds of 3 to 6 weeks of age was recorded for the first time in the Haldwani area of Nainital district (UP) in India in November, 1994. The overall mortality in 6 poultry farms was 61.62 per cent. The disease was experimentally transmitted by bacteria free infected liver homogenate extract passed through membrane filters of 0.22 and 0.1 mu APD. The aetiological agent was inactivated by heat treatment at 56 degrees C for one hour and 80 degrees C for 10 min. A precipitin band was demonstrated in agar gel immunodiffusion and counter immunoelectrophoresis using infected liver homogenate extract as antigen and homologous antisera raised in the laboratory. The disease was effectively controlled by formalinised and heat inactivated autogenous vaccine prepared from the infected livers of birds which died of natural infection.

  1. Lapointe, L., et al. (2002). “Antibody response to an autogenous vaccine and serologic profile for Streptococcus suis capsular type 1/2.” Can J Vet Res 66(1): 8-14.

An autogenous vaccine was developed, using sonicated bacteria, with a strain of Streptococcus suis capsular type 1/2. The objectives of this study were to evaluate the antibody response following vaccination and to assess the changes in antibody levels in pigs from a herd showing clinical signs of S. suis capsular type 1/2 infection in 6- to 8-week-old pigs. An enzyme-linked immunosorbent assay using the vaccine antigen was standardized. Results from a preliminary study involving 2 control and 4 vaccinated 4-week-old pigs indicated that all vaccinated pigs produced antibodies against 2 proteins of 34 and 43 kDa, respectively, and, in 3 out of 4 vaccinated pigs, against the 117-kDa muramidase-released protein. For the serologic profile, groups of 30 pigs from the infected herd were blood sampled at 2, 4, 6, 8, and 10 weeks of age. The lowest antibody level was observed between weeks 6 and 8, presumably corresponding to a decrease in maternal immunity. A marked increase was seen at 10 weeks of age, shortly after the onset of clinical signs in the herd. For the vaccination field trial, newly weaned, one-week-old piglets were divided into 2 groups of 200 piglets each (control and vaccinated); blood samples were collected from 36 piglets in each group at 2-week intervals for 12 weeks. A significant increase (P < 0.05) in antibody response was observed 4 weeks following vaccination and the level of antibodies stayed high until the end of the experiment. In the control group, the increase was only observed at 13 weeks of age, probably in response to a natural infection. The response to the vaccine varied considerably among pigs and was attributed, in part, to the levels of maternal antibodies at the time of vaccination. No outbreak of S. suis was observed in the control or vaccinated groups, so the protection conferred by the vaccine could not be evaluated.

  1. Marcove, R. C., et al. (1971). “A clinical trial of autogenous vaccine in osteogenic sarcoma in patients under the age of twenty-five.” Surg Forum 22: 434-435.
  1. Montague, F. E., et al. (1958). “The treatment of Chronic Osteomyelitis with autogenous vaccines.” Annals os Surgery 148(6): 925-930.

An apraisal of the results obtained with antibiotics in the treatment of osteomyelitis reveals that the primary hematogenous form of the disease has virtually been eliminated.3 The orbidity of the chronic form, however, is still a major problem on the Orthopedic Service of this hospital despite the use of effective surgical treatment and antibiotics. The magnitude of the problem is revealed in a study made by the Veterans Administration at the request of this hospital after a survey of the literature failed to supply such information (Table 1). It is obvious that chronic osteomyelitis is still a serious medical problem and that newer forms of therapy must be sought and investigated. Recently Waisbren 5 reported on the favorable use of gamma globulin and antibiotics in the treatment of bacterial infections including osteomyelitis which had failed to respond to maximum therapeutic efforts. The use of autogenous M. aureus vaccines has not played a role in the management of this disease since the advent of the antibiotic era. The study presented here concerns a therapeutic trial of autogenous vaccine therapy on six patients with intractable, chronic osteomyelitis of the lower extremities in conjunction with antibiotics and surgery. Particular reference is made to the immune response of these patients to a polysaccharide fraction of M. pyogenes var. aureus, and to the relationship of this response to the clinical progress of the patient with chronic osteomyelitis. An autogenous vaccine prepared to preserve optimal potency was instituted for this study over two years ago. The possibility that this vaccine might be more effective than previous standard M. aureus vaccines was not seriously considered until a review was undertaken of the records of these patients. When their case histories were compared with records of patients with similar injuries and infections from preceding years, a clinical impression was formed that these patients had done unusually well in the course of their disease. This report is a summary of the information available on these patients.

  1. Mouahid, M., et al. (1991). “Preparation and use of an autogenous bacterin against infectious coryza in chickens.” Vet Res Commun 15(6): 413-419.

An experiment was conducted to determine the efficacy of an autogenous bacterin against infectious coryza from a local strain of Haemophilus paragallinarum in Morocco compared with a commercial vaccine. Hens were vaccinated with a single dose or two doses of the bacterin at 15 and 18 weeks of age. Both the autogenous and the commercial vaccine conferred significant protection against experimental challenge (94% and 88%, respectively). A single dose was less protective with both vaccines.

  1. Murphy, et al. (1970). “Isolation of Mycoplasma from leukemic and nonleukemia patients. ” J Nat Cancer Inst 45: 243-251
  1. Pachauri, S. P. and R. C. Pathak (1969). “Bovine horn cancer: therapeutic experiments with autogenous vaccine.” Am J Vet Res 30(3): 475-477.
  1. Reeves, H. E., et al. (2013). “Evaluation of an autogenous vaccine in cattle against Escherichia coli bearing the CTX-M-14 plasmid.” Res Vet Sci 94(3): 419-424.

Enteric bacteria with resistance to third and fourth generation cephalosporin antibiotics, especially Escherichia coli bearing the blaCTX-M gene, have been detected in a wide range of food producing animals. However, commercial vaccines for these organisms are not currently available. An autogenous vaccine was prepared from E. coli bearing the blaCTX-M-14 gene and evaluated as a potential control measure to reduce shedding and dissemination of these organisms in cattle. Calves (n=30) received either an autogenous vaccine prepared from E. coli serotype O33 bearing the blaCTX-M-14 gene or a placebo by intramuscular injection on three separate occasions. Two weeks after the final vaccination, all calves were challenged by oral gavage with the O33 CTX-M-14 strain of E. coli (1×10(10) CFU). Faeces, intestinal mucosa and blood samples were taken for enumeration of total and CTX-M-14 E. coli and for assessment of the humoral immune response. The cumulative number of total E. coli excreted at 7 days post-challenge was significantly (p=0.006) lower in the vaccinated group than the placebo group. However, there was no significant difference in the shedding of either CTX-M-14 E. coli or total E. coli between vaccinated and placebo calves throughout the study period. The systemic immune response to E. coli O33 antigen was tested by ELISA and was significantly higher (p<0.001) in vaccinated than placebo calves. However, there was no significant difference in the mucosal immune response. These findings do not support the use of autogenous vaccination for the control of CTX-M-14 E. coli in calves.

  1. Rosales-Mendoza, S. (2013). “Future directions for the development of Chlamydomonas-based vaccines.” Expert Rev Vaccines 12(9): 1011-1019.

Besides serving as a valuable model in biological sciences, Chamydomonas reinhardtii has been used during the last decade in the biotechnology arena to establish models for the low cost production of vaccines. Antigens from various pathogens including Plasmodium falciparum, foot and mouth disease virus, Staphylococcus aureus, classical swine fever virus (CSFV) as well as some auto-antigens, have been produced in C. reinhardtii. Although some of them have been functionally characterized with promising results, this review identifies future directions for the advancement in the exploitation of this robust and safe vaccine production platform. The present analysis reflects that important immunological implications exist for this system and remain unexplored, including the possible adjuvant effects of algae biomolecules, the effect of bioencapsulation on immunogenicity and the possible development of whole-cell vaccines as an approach to trigger cytotoxic immune responses. Recently described molecular strategies that aim to optimize the expression of nuclear-encoded target antigens are also discussed.

  1. Ruso, S., et al. (2015). “Bacterial vaccines in chronic obstructive pulmonary disease: effects on clinical outcomes and cytokine levels.” APMIS 123(7): 556-561.

Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity worldwide. Exacerbation episodes impair lung function leading to disease progression. Levels of inflammation markers correlate with disease severity. Bacterial immunomodulators have shown a beneficial effect in COPD, improving symptoms and reducing the rate of exacerbations. This is an observational prospective study on 30 patients diagnosed with bronchiectasis and COPD, who received bacterial autogenous vaccine for 12 months. The rate of exacerbation, severity of symptoms and lung function were studied at baseline and after treatment. In addition, plasma levels CRP, IL6, IL8, and TNFalpha were measured. After treatment we found a reduction in mean acute respiratory infections and signs of lung disease. Acute phase proteins IL6 and CRP increased in blood and IL8 decreased. These changes may be related to the repeated injection of inactivated bacteria. Given the implication of these factors in the pathogenesis of COPD, particularly the production of IL8, the causes and consequences of cytokine modulation by bacterial vaccines should be investigated. Vaccination with autogenous vaccines for 1 year can produce a significant clinical improvement in COPD patients, reducing the frequency of exacerbations associated to changes in the profile of markers of inflammation.

  1. Ruso, S., et al. (2015). “Bacterial vaccines in chronic obstructive pulmonary disease: effects on clinical outcomes and cytokine levels.” APMIS 123(7): 556-561.

Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity worldwide. Exacerbation episodes impair lung function leading to disease progression. Levels of inflammation markers correlate with disease severity. Bacterial immunomodulators have shown a beneficial effect in COPD, improving symptoms and reducing the rate of exacerbations. This is an observational prospective study on 30 patients diagnosed with bronchiectasis and COPD, who received bacterial autogenous vaccine for 12 months. The rate of exacerbation, severity of symptoms and lung function were studied at baseline and after treatment. In addition, plasma levels CRP, IL6, IL8, and TNFalpha were measured. After treatment we found a reduction in mean acute respiratory infections and signs of lung disease. Acute phase proteins IL6 and CRP increased in blood and IL8 decreased. These changes may be related to the repeated injection of inactivated bacteria. Given the implication of these factors in the pathogenesis of COPD, particularly the production of IL8, the causes and consequences of cytokine modulation by bacterial vaccines should be investigated. Vaccination with autogenous vaccines for 1 year can produce a significant clinical improvement in COPD patients, reducing the frequency of exacerbations associated to changes in the profile of markers of inflammation.

  1. Schijns, V. E., et al. (2015). “First clinical results of a personalized immunotherapeutic vaccine against recurrent, incompletely resected, treatment-resistant glioblastoma multiforme (GBM) tumors, based on combined allo- and auto-immune tumor reactivity.” Vaccine 33(23): 2690-2696.

Glioblastoma multiforme (GBM) patients have a poor prognosis. After tumor recurrence statistics suggest an imminent death within 1-4.5 months. Supportive preclinical data, from a rat model, provided the rational for a prototype clinical vaccine preparation, named Gliovac (or ERC 1671) composed of autologous antigens, derived from the patient’s surgically removed tumor tissue, which is administered together with allogeneic antigens from glioma tissue resected from other GBM patients. We now report the first results of the Gliovac treatment for treatment-resistant GBM patients. Nine (9) recurrent GBM patients, after standard of care treatment, including surgery radio- and chemotherapy temozolomide, and for US patients, also bevacizumab (Avastin), were treated under a compassionate use/hospital exemption protocol. Gliovac was given intradermally, together with human GM-CSF (Leukine((R))), and preceded by a regimen of regulatory T cell-depleting, low-dose cyclophosphamide. Gliovac administration in patients that have failed standard of care therapies showed minimal toxicity and enhanced overall survival (OS). Six-month (26 weeks) survival for the nine Gliovac patients was 100% versus 33% in control group. At week 40, the published overall survival was 10% if recurrent, reoperated patients were not treated. In the Gliovac treated group, the survival at 40 weeks was 77%. Our data suggest that Gliovac has low toxicity and a promising efficacy. A phase II trial has recently been initiated in recurrent, bevacizumab naive GBM patients (NCT01903330).

  1. Shipkowitz, N. L., et al. (1967). “Evaluation of an autogenous laryngeal papilloma vaccine.” Laryngoscope 77(6): 1047-1066.
  2. Smith, R. et al. (2000). “Neurologic manifestations of Mycoplasma pneumonia infections: diverse spectrum of diseases. A report of six cases and review of the literature.” Clin Pediatr 39(4): 195-201.
  1. Southam, C. M., et al. (1972). “Proceedings: Clinical trial of autogenous tumor vaccine for treatment of osteogenic sarcoma.” Proc Natl Cancer Conf 7: 91-100.
  1. Ssenyonga, G. S., et al. (1990). “Therapeutic value of partial excision of lesions combined with administration of an autogenous vaccine during an episode of cutaneous papillomatosis in cattle of Uganda.” J Am Vet Med Assoc 197(6): 739-740.

The therapeutic value of partial excision of lesions combined with administration of an autogenous vaccine in calves during an episode of cutaneous papillomatosis was evaluated. Of 10 Holstein calves naturally infected with cutaneous papillomatosis, 5 were given 20 ml of autogenous vaccine in addition to undergoing partial excision of the lesions; the other 5 calves were not given vaccine. Results indicate that partial excision combined with administration of autogenous vaccine has some therapeutic value in calves with small pedunculated papillomas, but not in calves with large confluent lesions.

  1. Senyonga, G. S., et al. (1990). “Therapeutic value of partial excision of lesions combined with administration of an autogenous vaccine during an episode of cutaneous papillomatosis in cattle of Uganda.” J Am Vet Med Assoc 197(6): 739-740.

The therapeutic value of partial excision of lesions combined with administration of an autogenous vaccine in calves during an episode of cutaneous papillomatosis was evaluated. Of 10 Holstein calves naturally infected with cutaneous papillomatosis, 5 were given 20 ml of autogenous vaccine in addition to undergoing partial excision of the lesions; the other 5 calves were not given vaccine. Results indicate that partial excision combined with administration of autogenous vaccine has some therapeutic value in calves with small pedunculated papillomas, but not in calves with large confluent lesions.

  1. Stephens, C. B., et al. (1979). “Autogenous vaccine treatment of juvenile laryngeal papillomatosis.” Laryngoscope 89(10 Pt 1): 1689-1696.

Seventeen cases of juvenile laryngeal papillomatosis have been seen and treated with microlaryngoscopy, removal of papillomas, and administering of autogenous vaccine. Holinger’s original findings could be confirmed. The operation frequency of 9 patients was significantly reduced, 5 were improved, and 3 unchanged. In no case was an undesirable reaction to the vaccine observed. Electron microscopy showed no virus-like particles in the papilloma but a section of a vulvar wart did show the virus.

  1. Thachil, A. J., et al. (2007). “Application of polymerase chain reaction fingerprinting to differentiate Ornithobacterium rhinotracheale isolates.” J Vet Diagn Invest 19(4): 417-420.

Ornithobacterium rhinotracheale (ORT) is an infectious respiratory pathogen of chickens, turkeys, and wild birds. There are 18 serotypes of ORT reported worldwide. In this study, enterobacterial repetitive intergenic consensus (ERIC) polymerase chain reaction and random amplified polymorphic DNA assay with Universal M13 primer-based fingerprinting techniques were investigated for their ability to differentiate ORT isolates. The authors examined 50 field isolates and 8 reference strains of ORT for their genetic differences. The fingerprint patterns were compared with serotyping results of ORT by the agar gel precipitation test. M13 fingerprinting revealed different patterns for 6 reference serotypes of ORT that were tested, namely, C, D, E, I, J, and K. Ornithobacterium rhinotracheale reference serotypes A and F yielded indistinguishable fingerprints with M13 fingerprinting. The ERIC 1R technique discerned only 5 of the 8 reference serotypes of ORT. Distinct fingerprints were also found within the ORT serotypes with both techniques. From 58 isolates of ORT that were fingerprinted belonging to 8 ORT serotypes, 10 different fingerprints were obtained with M13 fingerprinting and 6 different fingerprints were obtained with ERIC 1R fingerprinting. M13 fingerprinting technique was found to be more discriminative in differentiating ORT isolates than the ERIC 1R fingerprinting technique. These results suggest that fingerprinting techniques may be a more discerning tool for characterizing ORT isolates than the serological test using the agar gel precipitation test. This fingerprinting technique could potentially be a valuable tool in identifying an isolate from a clinical outbreak of ORT infection for development of an autogenous vaccine.

  1. Theilen, G. H., et al. (1977). “Chemoimmunotherapy for canine lymphosarcoma.” J Am Vet Med Assoc 170(6): 607-610.

A total of 157 dogs with lymphosarcoma were available for study; 67 were treated. All of the treated dogs were given 4 drug combinations and 20 of them also were given autogenous vaccine. Sixty (90%) of the dogs treated with multiple drugs improved clinically. Of the dogs with clinical improvement, 48 (80%) had either complete or partial remission; of these, 32 (67%) had complete remission. Clinical staging proved useful in increasing the accuracy of prognosis, whereby dogs in less advanced stages of disease responded better to therapy, with a higher percentage of complete clinical remissions and longer survival. The mean survival time of the 47 dogs treated with drugs alone was 138 days, which compared with a mean survival time of 30 days for 34 nontreated dogs. Dogs subjected to chemotherapy and immunotherapy had a mean survival time of 341 days. Dogs in complete remission at time of vaccination survived significantly (P less than 0.01) longer than did dogs treated with drugs and vaccinated while not incomplete remission.

  1. Vielitz, E., et al. (1992). “[Immunizing against salmonella infections with live and inactivated vaccines].” Dtsch Tierarztl Wochenschr 99(12): 483-485.

A live attenuated auxotrophic S. typhimurium (S. tm.)-mutant was used by orally administration via drinking water several times during rearing, combined with 1- or 2-times parenteral injection of an autogenous S. enteritidis (S. e.)/S. tm.-oil emulsion vaccine. In a 8-month period, more than 500,000 birds were vaccinated. The vaccine was safe. Challenge test showed protection in the vaccinates and their offspring. The number of isolates in the farms detected by regular monitoring decreased. The protection of the live-culture mutant lasted about only 8 to 10 weeks. A. S. tm.-mutant more potent for chickens will be tested now. We consider vaccinations as one important factor in a salmonella control program, especially for commercial layers and broiler breeders.

  1. Villumsen, K. R., et al. (2015). “Adverse and long-term protective effects following oil-adjuvanted vaccination against Aeromonas salmonicida in rainbow trout.” Fish Shellfish Immunol 42(1): 193-203.

Prophylactic measures against Aeromonas salmonicida subsp. salmonicida, the causative agent of furunculosis, have been an active field of research for decades, with studies mainly focused on Atlantic salmon (Salmo salar). In the present study we have examined the protective and adverse effects of mineral oil-adjuvanted injection vaccines on rainbow trout (Oncorhynchus mykiss). A commercial vaccine and an experimental auto vaccine, as well as their respective adjuvant formulations alone were used to evaluate their individual effects, both prior to and during an experimental waterborne infection challenge. Macro- and microscopic examination revealed signs of vaccine-induced adverse effects from 10 weeks to 14 months post vaccination. Both vaccines induced statistically significant protection during the experimental challenge (P=0.018 for both vaccines), as well as significantly elevated levels of specific circulating antibodies prior to and during the experimental challenge when compared to an unvaccinated control group. During the early, critical time points of the infection, both vaccines appeared to protect against pathological changes to the liver and spleen, which provides a probable explanation for the reduced mortality seen in the vaccinated groups. A significant correlation was found between the level of A. salmonicida-specific antibodies measured prior to challenge and the endpoint survival of each group after the experimental infection, and furthermore, the levels of these antibodies remained elevated for at least 14 months post vaccination.

  1. Wallenborn, P. A., Jr. (1976). “Papillomas of the larynx and pharynx: two case reports.” Laryngoscope 86(11): 1663-1668.

Two unusual cases of papillomas are presented: the first is that of a young boy with extensive papillomas of the larynx who was treated successfully without tracheotomy using endolaryngeal surgery and steroids at the time of each procedure. This case adds to the clinical evidence that the most probable cause of juvenile papillomas is a virus, since the mother had condyloma acuminata during pregnancy and at term. The second case is that of a young girl with rapidly recurring papillomas of the mouth and pharynx who was treated successfully with an autogenous vaccine and cryosurgery after other measures failed. This case demonstrates the effectiveness of cryosurgery in the treatment of papillomas and the possible efficacy of the autogenous vaccine suggests a viral etiology for papillomas of the pharynx and larynx.

  1. Weber, A. and D. Gobel (1995). “[Treatment of chronic diarrhea in dogs and cats under field conditions using oral E. coli vaccines].” Tierarztl Prax 23(1): 80-82.

An autogenous oral E. coli vaccine was tested for efficacy in the treatment of chronic diarrhoea in dogs (n = 82) and cats (n = 50) under field conditions. The data were collected through evaluation of questionnaires completed and returned by veterinarians. After oral application of the E. coli vaccine the symptoms of diarrhoea were stopped in 71% of the treated animals within two to five days. In further 15% of the cases the enteric symptoms continued but were not so severe as in the beginning of the treatment. There was no therapeutic success with the oral E. coli vaccine in further 14% of the animals in cause of food allergy, ascariasis, volvulus or pancreatic insufficiency.