VAFSTFLOG.GIF (4046 bytes)

Vaccine-Associated Feline Sarcoma Task Force Continues, Receives Funding for Additional Studies

As of July 2000, the Vaccine-Associated Feline Sarcoma Task Force (VAFSTF) has received a total of $693,353 to fund research into the incidence, etiology, and treatment of vaccine-associated feline sarcomas. The Task Force extends its gratitude to the professional organizations and feline biologics and pharmaceuticals manufacturers who have generously supported its research and educational efforts. Pfizer Animal Health again leads the way during the 1999-2000 funding cycle with its contribution of $100,000, Pfizer’s second consecutive Platinum level contribution. Other manufacturers include Novartis and Fort Dodge Animal Health, each contributing at the Silver level of $25,000 during this funding cycle. Schering-Plough Animal Health, Intervet, and Merial Animal Health made contributions of $10,000 each. Professional organizations contributing to this year’s studies include the Veterinary Cancer Society, the Cornell Feline Health Center, and the American Association of Feline Practitioners, who each donated $10,000. Donations for 1999-2000 total $210,000.

Activities to Continue

Formed in late 1996, the VAFSTF was originally conceived by the sponsoring organizations (AVMA, AAHA, AAFP, and VCS) to be a three-year effort. The Task Force has now restructured to become self-supporting and continue its work for at least two more years. The Task Force is preparing a white paper for release later this summer to assess the VAFSTF study findings to date.

Following is a brief description of the five studies approved during the 1999 – 2000 funding cycle.

Etiology Studies

  1. Selective inhibition of platelet-derived growth factor receptor (PDGFR) activity, 2-year study.

Research conducted in the investigators’ laboratory has shown that vaccine-associated feline sarcomas express high levels of a growth factor receptor for platelet-derived growth factor (PDGF). The investigators have found that this growth factor stimulates cells to grow in tissue culture, indicating that it may be one of the dominant factors associated with this cancer. They plan to test a drug to inhibit activity of the PDGF receptor and determine if blocking the receptor inhibits tumor growth. In addition, they will express a mutant receptor in feline cancer cells and determine if this will help inhibit activation of the normal PDGF receptor. The results of this study will help determine if the PDGF receptor contributes to the growth and progression of this aggressive cancer.

Principle investigator is E. Gregory MacEwen, VMD. Co-investigators are J. Carew and R. Radinsky

  1. Defining the role of the oxidative DNA lesion, 8-hydroxyguanine, in vaccine-associated feline sarcoma.
  2. A basic principle of cancer is that it cannot occur without some interaction with the genetic material of the body DNA. The purpose of this project is to uncover the initial step in the causation of aggressive soft tissue cancers in cats that may be associated with routine administration of vaccines. Since vaccines often cause an inflammatory reaction at the site of injection, highly reactive oxygen-derived free radicals are generated locally that may in some way alter the DNA of certain cells. The investigators will vaccinate a group of cats with commercially available vaccines at three different sites, then determine the concentration of a DNA alteration known as 8-hydroxyguanine that develops at these sites. They will also study this alteration in client-owned cats that develop inflammatory reactions approximately 3 weeks after vaccination. It is hoped that this work will lead to the development of a test to help determine which vaccine components may be causing vaccine-associated sarcomas. Re-formulation of vaccines may then prevent development of these cancers.

    Principle investigator is J. McHugh Law, DVM, PhD, DACVP. Co-investigators are M. Hauck and S. Price

  3. Evaluation of mutagenicity of feline vaccines using AL assay: Year 2, 15-month study.
  4. Little is known about the etiopathogenesis of vaccine-associated sarcomas, but the probability of tumor development seems higher when adjuvanted vaccines have been administered. The investigators hypothesize that adjuvanted vaccines currently in use are inherently mutagenic to mammalian cells as a result of oxidative damage to DNA. In the first year of their research, the investigators used an in vitro assay, called the AL assay, to evaluate the toxicity and mutagenicity of some commonly used feline vaccines. Because adjuvanted vaccines were found to be more toxic and mutagenic than non-adjuvanted vaccines, the researchers plan to continue this line of investigation. They also hypothesize that cats that develop vaccine-associated sarcomas are more susceptible to oxidative damage than are other cats. This hypothesis will be investigated by comparing the anti-oxidant capacity of affected cats with that of unaffected cats.

    Principle investigator is Susan M. LaRue, DVM, PhD. Co-investigator is E. A. McNiel.

  5. Molecular biomarkers of vaccine-associated feline sarcoma: characterization of a genetic predisposition.

The investigators are studying key molecular changes that occur during the development of vaccine-associated feline sarcomas, with the ultimate goal of improving strategies for disease prevention and management. Initial results indicate that there may be a heritable genetic component that makes some cats more prone to tumor development. In the next phase of study, the researchers will analyze specific breeds of cats in the US that may have this predisposition. The results of this investigation will hopefully enable informed decisions to be made regarding the breeding and care of cats with the susceptibility to developing vaccine-associated sarcomas.

Principle investigator is Sagarika Kanjilal, PhD. Co-investigators are V. Kapur, J. S. Klausner, and C. Wood.

Treatment Study

  1. Idiotypic immunization with anti-P53 monoclonal antibody as adjuvant therapy for P53 positive feline vaccine- associated sarcoma; Aim 1A.

Vaccine-associated feline sarcomas, like all cancers, ultimately have a genetic basis. One gene that is mutated in these tumors, p53, normally functions to suppress tumor cell growth. The mutated p53 gene codes for an abnormal protein, and antibodies exist that recognize and stick to the abnormal protein. Because abnormal p53 protein is present in the majority of vaccine-associated sarcomas, it may serve as a widely conserved target for therapy. This study will investigate the potential of eliciting immune responses against abnormal p53 in hopes that the affected cat’s own immune system can be recruited to help combat the cancer.

Principle investigator is A. Elizabeth Hershey, DVM. Co-investigator is S. C. Helfand.

 

The VAFSTF is an alliance of four national veterinary organizations (AAFP, AAHA, AVMA, and VCS) along with representatives from academia, industry, and USDA-APHIS. For continued updating on the activities of the VAFSTF, monitor the task force's Web site at http://www.avma.org/vafstf.

Submitted by Dr. James R. Richards
Education/Communication Subgroup Chair, VAFSTF
Director, Cornell Feline Health Center
Cornell University College of Veterinary Medicine

    

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