As I am a veterinary oncologist, one of fewer than 400 in the world, many readers may be scratching their heads, thinking, "Did I just read that?," but in fact, veterinary oncology is a sought-after residency in veterinary medicine, that just like human oncology, is defined by "hope." Despite chemotherapy protocols using many of the same drugs, dose intensity and dose frequency are reduced so that there is no compromise in quality of life. We do not make any animal sick just to keep them alive. The once "backyard pet" is now part of the nuclear family to many people, and for that reason, options for cancer treatment are very much in demand in veterinary medicine.
To that end, there is tremendous interest in immunotherapy, and we are fortunate to be involved in a progressive clinical opportunity for pets diagnosed with cancer.
The Veterinary Specialty Center of the Hudson Valley (http://www.vschv.com) is investigating the efficacy of treating naturally occurring dog and cat cancers with a genetic DNA telomerase cancer vaccine followed, by DNA vaccination using a plasmid encoding telomerase. The non-funded study, which is led by the veterinary research team of Dr. Luigi Aurisicchio from Takis, Dr. David Jemiolo from Vassar College, and myself, will enroll dogs and cats with various cancers including lymphosarcoma, hemagiosarcoma, carcinomas, and others in a non-placebo controlled study.
With many dogs and cats over the age of 10 diagnosed with cancer, it is a goal of the research team to establish treatments to improve therapeutic options. Current cancer treatments in domestic animals focus on surgery, radiation therapy, chemotherapy to attenuate metastatic expansion, and palliative management to control the symptoms of the cancer.
Immunotherapy has been limited and still remains in the early stages for therapeutic intervention. Chemotherapy is most common and often provides an initial level of control, but eventually resistant cells expand clonally and metastasize.
As Dr. Steven Crow, Medical Oncologist at VCA Sacramento Veterinary Referral Center, says, "We have been treating canine lymphoma with various combinations of the same five drugs for more than 40 years with only modest improvements in remission and survival duration. In view of the tremendous improvement in prognosis for Hodgkin's disease and ALL in children, it is disappointing and frustrating that we are not curing many dogs with lymphoma. The addition of half-body radiation therapy and the burgeoning availability of stem cell transplantation in private specialty practices are welcome additions; however, those treatments are too costly for most pet owners. We need something cheaper and better."
Telomerase Vaccine
The use of a telomerase vaccine targets a protein whose enhanced expression is a common characteristic present in 85 to 95 percent of both human and animal cancer cells. Telomerase is not expressed in most differentiated cells, making it an ideal target for cancer therapeutics. Upregulated telomerase allows for limitless replication, thus "tricking" the cell to avoid apoptosis (programmed cell death) in lieu of continued replication of a malignant oncogene. Our goal specifically in canine lymphosarcoma patients is to obtain clinical, and preferably molecular remission with standard of care chemotherapy and then follow with the vaccine.
Therapeutic vaccines are an important progressive approach which, when combined with other therapies, can improve long-term control of cancer. A variety of immunization technologies are being explored. Among them, genetic (DNA-based) vaccines are emerging as promising methodologies to induce immune responses against a wide variety of tumor antigens, including telomerase.
Recent findings show that combinations of different modalities of immunization (heterologous prime/boost) are able to induce superior immune reactions as compared with single-modality vaccines. Our investigational vaccine harnesses this type of innovative combination.
Genetic vaccines are not new, but newer methods to improve greater DNA uptake has led to in-vivo electroporation (DNA-EP). Inoculating plasmid DNA encoding for a protein antigen by means of a simple intramuscular or intradermal injection currently offers a vaccine approach that is easily performed, safe for host, and relatively inexpensive. However, since target cells lack the co-stimulatory molecules needed as part of the CTL activation process, DNA vaccination is in general poorly efficient unless an inflammatory stimulus is applied in parallel.
This mode of administration through DNA-EP will allow maintenance of anti-tumor immunity. This approach uses brief electrical pulses that create transient "pores" in the cell membrane, thus allowing large molecules such as DNA or RNA to enter the cell cytoplasm. Immediately following cessation of the electrical field, these pores seal and the molecules are trapped in the cytoplasm without causing cell death.
"Tissue harvested from cancer cells will be evaluated for telomerase expression via RT-PCR," Dr. Jemiolo says. "Our relationship with VSCHV provides a valuable clinical and laboratory experiences for our students. They are working on problems of cancer treatment and management whose solutions will provide valuable information for clinical patients. In addition, VSCHV offers them the opportunity to participate in this cutting-edge cancer treatment study. Nowhere else outside of a veterinary teaching hospital does this relationship exist in veterinary specialty medicine."
21st Patient
VSCHV plans to study these therapies over the next five years with a focus toward grant approvals and clinical/commercial availability. As of now, the research team has their 21st patient.
We are in the early stages of some exciting research with a new technique that gives hope to our cancer patients. Published research from Europe on the treatment of canine lymphosarcoma with this same vaccine has shown improved overall survival times vs. standard of care. Whether it is the vaccine or another variable, it is not clear, but our studies will determine that while helping treat patients along the way.1
Additional information can be found on our website: http://www.vschv.com