Now there's a vaccine for Malignant Melanoma......what this means for your canine...........
Dogs with advanced malignant melanoma may now survive longer when they are vaccinated with a new vaccine containing human DNA. Also, the vaccine provides a springboard for evaluating other human DNA vaccines in the management of other canine cancers.
Philip J. Bergman, D.V.M., PH.D, DACVIM, head of the Donaldson-Atwood Cancer Clinic at the Animal Medical Center in New York, found in the recent canine cancer trial that despite having advanced malignant melanomas, the dogs in the study lived an average of 389 days following the vaccination, compared to a maximum of about 150 days for dogs receiving standard therapies of chemotherapy and radiation. Bergman says "Cancer immunotherapy involves breaking tolerance to tumors. The DNA vaccine used in this study was an extremely pure form of human DNA".
While melanomas in humans are typically associated with skin cancer, melanoma can present itself anywhere in dogs. Most canine melanomas that appear in areas with hair are benign.....whereas those that appear in the mouth, footpads, lips, eyes and toes are most likely to be malignant and aggressive. Aggressive canine tumors appear to be very similar to aggressive human melanoma because both are resistant to chemotherapy and radiology and both are very fast growing. Such tumors spread to the same sites, such as the lungs, lymph nodes, liver and brain.
Canine malignant melanoma (CCM) represents about 4% of all canine tumors (regardless of breed type) and is the most common oral tumor in dogs.
The trial conducted from April to December 2002, included dogs. It was published in the April 2003 issue of Clinical Cancer Research. This study involved collaboration among scientists at the Animal Medical Center and Memorial Sloan-Kettering Cancer Center, a human cancer facility...both of which are in New York. Dr. Bergman, who is an adjunct associate faculty member at Memorial Sloan-Kettering, worked closely with Jedd Wolchok.....M.D., PH.D, who leads the DNA vaccine program at Sloan-Kettering, in coordinating the study and obtaining human DNA for the trial.
Dr. Bergman says, "Part of what made this trial special is that we used pet dogs". These were inbred dogs with competent immune systems that developed spontaneous synergetic (in the same species) melanoma....exactly the way humans develop the cancer. Along with the fact that dogs live in the same environment as humans, this makes the dog the most faithful clinical model for human melanoma when compared with the mouse". Dr. Bergman also concludes that "Both dogs and humans may benefit from this cancer research."
When using mice, studies showed that vaccination with DNA-encoding cancer differentiation antigens is ineffective when self-DNA is used.....but when DNA from another species is used, effective tumor immunity can be induced. Mouse studies also demonstrated that xenogenetic (in a different species) DNA vaccination with genes encoding tyrosinse family members (a family of proteins that are used to make black pigment) can induce antibody and cytotoxic T-cell (T lymphocytes responsible for killing another cell, such as bacteria) responses, resulting in tumor rejection in both pre-existing and future tumors. These mouse studies also provided the rationale for a trial of xenogenetic DNA vaccination in CMM using the human tyrosinase gene.
DNA vaccination bypasses some of the hurdles generally involved in vaccine development because it is relatively inexpensive and simple to purify in a large quantity. However, using DNA vaccines to vaccinate against cancer cells proved more difficult than using DNA to induce immune responses to viral proteins.
The scientists found that one way to induce immunity against a tissue-specific differentiation antigen on cancer cells is to vaccinate with xenogenetic antigen or DNA that is homologous (similar) to the cancer antigen.
Dr. Bergman states that "We chose defined melanoma differentiation antigens of the tyrosinase family. Tyrosinase is a melanosomal glycoprotein (a substance made by the body that has carbohydrate and protein aspects) that is essential in melanin synthesis. Xenogenetic DNA vaccination induced tumor protection from xenogenic melanoma challenge and autoimmune hyperpigmentation."
The cancer trials included two Cocker Spaniels, a Siberian Husky, a Lhasa Apso, a Bichon Frise', a German Shepherd dog and three mixed breed dogs with advanced stage II, III, or IV malignant melanoma.
Five dogs had primary malignant melanoma in the mouth; three had nail bed or footpad malignant melanoma and one dog had a high-grade melanoma in its eye.
Dr. Bergman said, "From the results of this study, we can conclude that xenogenetic human tyrosinase DNA vaccination of dogs appears to be safe, based on minimal toxicity and no system toxicity, and potentially efficacious, based on clinical anti-tumor responses and remarkably prolonged median survival."
Vaccination immunotherapy using human DNA is being considered as a potentially therapeutic form of cancer management warranting evaluation in other canine cancers. For example, scientists plan to study a vaccine that contains PSMA, which is found in men with prostate cancer and is expressed in the blood supply of certain canine tumors. It also has the ability to attack the blood system when tumors are expressed. Dr. Bergman says they will be looking at a vaccine containing different species of DNA in managing canine lymphoma.
The results of the CMM cancer trial also prompted additional evaluation of the novel therapeutic approach in CMM and advanced human melanoma. Dr. Bergman and his colleagues are now in their fourth cancer trial. "We hope to apply for commercial approval to use this vaccine in the next few months", he says.
"It's a slow and arduous process, but the pace helps to ensure that the vaccine is efficacious and safe".
Owners of dogs who have stage II, III, IV malignant melanomas who are interested in taking part in Dr. Bergman's vaccination studies may contact him at :
THE ANIMAL MEDICAL CENTER IN NEW YORK
(212) 329-8674 or you may email him at: Philip.bergman@amcyn.org
Owners must be able to bring their dogs to the AMC for five biweekly veterinary visits and those who live more than 50 miles from AMC must pay about $2,500 for x-rays, examinations and blood tests. There is no cost for the vaccines.
