In the early 1990s, veterinarians became aware that some cats developed sarcomas at the infection sites used to administer vaccines. This could have started a widespread panic, with people refusing to give their cats the protective shots, but this did not happen, partly because of the Vaccine-Associated Feline Sarcoma Task Force.
"One of the biggest things the task force has achieved is to take a potential public relations disaster and turn it around into a means of funding a lot of really good research," said Dr. Robin Starr, chair of the task force that was formed in 1996 to investigate the issue. The task force funded research that has led to new insights into the mechanisms of the disease, as well as potential preventive measures and therapies.
Dr. Elizabeth McNiel, an assistant professor in the Department of Small Animal Clinical Science at the University of Minnesota, is principal investigator of one of three studies that received funding last year. Her team has evaluated nine commercially available vaccines so far and has found that most of the adjuvant products induce cell mutations in test tube studies.
"We are now looking at ways in which vaccines might be able to cause DNA damage and mutation," Dr. McNiel said. "We have some evidence that it is due to the production of oxygen radicals in cells and that vaccines induce the production of oxygen radicals."
Another study, led by Dr. Kenneth Rassnick, assistant professor of medical oncology at Cornell University, is evaluating the efficacy and toxicity of ifosfamide, which is used to treat the tricky sarcomas. Since poorly defined tumors, such as sarcomas, make complete removal almost impossible, researchers hope that chemotherapeutics can provide a safe treatment avenue. At press time, 11 cats were enrolled in the trial and researchers had begun treatment and monitoring.
The third study funded last year, led by Sagarika Kanjilal, PhD, an assistant professor in the Department of Veterinary Pathobiology at the University of Minnesota, is examining key molecular changes that occur during tumor development. Evidence suggests that genetics may dictate which cats are prone to develop cancer. Dr. Kanjilal and her colleagues have analyzed breeds of cats that may have this predisposition and are now investigating the entire set of genes that are differentially expressed during tumor development.
| Courtesy of Dr. Barbara Corn|
Several contributors funded the 2000-2001 studies, including Pfizer Animal Health, Fort Dodge Animal Health, Biocor Animal Health, American Association of Feline Practitioners, Cornell Feline Health Center, and Intervet Inc.
Studies funded in previous years have explored other avenues and provided other insights. We now know, for instance, that vaccine-induced sarcomas are associated with a loss of heterozygosity of the p53 gene, a gene that normally controls programmed cell death. This dysregulation can contribute to unrestricted growth and survival of cells, and it has been implicated in a variety of cancers in people.
We also know that inappropriate amounts of platelet-derived growth factor can transform normal fibroblasts into sarcoma cells. Another study testing the promising, chemoprotective agent liposome-encapsulated doxorubicin found that in order to avoid unacceptable rates of delayed toxicoses, the dosage has to be reduced.
Whereas some studies opened up new avenues for research, others narrowed the possibilities needing attention. Preliminary results indicate that, unlike some scientists thought, papillomavirus, herpesvirus, and polyomavirus don't play a role in the development of vaccine-associated sarcomas.
Researchers are optimistic about the progress thus far and have high hopes for the future. "If you look at the decades that have gone into research in cancers in humans with tremendously greater amounts of funding," commented Dr. Starr. "We have done very well."