Always Striving to Break New Ground in Veterinary Cancer Care at VOSRC
Equine Melanoma Vaccine
Equine melanoma is a disease that is relatively common, particularly in gray horses. Many times, these tumors are harmless; however, some can be aggressive. In these cases, melanoma can be a very serious disease. The research laboratory on site at VOSRC in West Chester has an ongoing program of processing equine melanoma tumors into vaccines as part of a program for controlling and minimizing the effects of this illness (Jeglum, 1997).
Equine Melanoma as a Model for Human Melanoma Progression
We have established a new collaboration using horse melanoma as a model for studying the mechanisms of melanoma progression. This work is being conducted in the laboratory of Dr. Ashani Weeraratna, who is Ph.D. scientist in molecular and cellular oncology. Her staff scientist, Dr. Michael O’Connell, summarizes the collaboration:
In our group, we study the mechanisms of melanoma progression. We have identified several molecules that may be important in mediating melanoma progression and pursued these data to dissect the important pathways by which these molecules signal. Our current data indicates that one such molecule, Wnt5A, is both an important player in melanoma progression and possibly mediates the escape of tumor cells from immune surveillance. It appears to initiate these effects via an orphan tyrosine kinase receptor, ROR2, and we are currently evaluating the therapeutic potential of this molecule. In addition, we continue to explore paradigms of tumor metastasis from other angles, such as in the context of the microenvironment.
Studies have shown that as melanoma progresses tumor pigmentation is lost. That loss has been attributed to a decrease in expression of markers such as pigment epithelium derived factor (PEDF), melanoma antigen recognized by T-Cells 1 (MART-1), and premelanosome protein (PMEL; also known as gp100). Ongoing projects include studying how the Wnt5A/ROR2 pathway contributes to loss of pigmentation and the subsequent metastatic progression of human melanoma.
As equine melanoma is similar to human melanoma, and due to the observation that loss of pigmentation in these animals leads to melanoma development and progression, we propose to investigate the “pigmentation pathway” in equine melanoma progression. In order to pursue this we are in need of fresh skin and tumor biopsies (from the same animals). In animals that have metastatic disease, biopsies of both the primary and the metastatic tumors would be needed. Images of the animals (full view and close up) to match pigmentation to tumors samples would also be useful. From these samples, immunohistochemical/fluorescent studies, protein and RNA analysis for pigmentation and metastatic markers, and the establishment of cell lines for invasion assays will be performed.
Genetic Epidemiology of Cancer in Golden Retrievers
VOSRC has collected pedigrees on more than 500 golden retrievers with cancer since the 1980s, resulting in a family of more than 4,000 dogs. Recently, this work allowed VOSRC to report on the inheritability of lymphoma and soft tissue sarcomas in the breed (Theilan Symposium, 2009). This is an ongoing project with blood samples being collected for collaboration with geneticists at North Carolina State University (M. Breen) and The Broad Institute (K. Lindblad-Toh). We continue to map the affected dogs for risk factors to be evaluated and for potential breeding planning.
Novel Treatments of Canine Lymphoma and Osteosarcoma
We are collaborating with Dr. Nicola Mason from the University of Pennsylvania to look for a novel approach in overcoming drug resistance in canine lymphoma.
A Phase I Clinical Trial to Evaluate the Effects of NBD Peptide in Dogs With Diffuse Large B Cell Lymphoma
Lymphoma is a cancer of white blood cells that occurs commonly in dogs. Chemotherapy is used to treat lymphoma and about 85% of dogs respond well to this treatment. However, the majority of dogs will relapse with clinical disease within one year of diagnosis and treatment. One potential reason for disease recurrence is the presence of drug-resistant lymphoma cells that are not killed by chemotherapy. Researchers at Penn Vet have identified an aberrantly active, intracellular pathway within lymphoma cells that promotes cancer cell survival and proliferation. Results of a pilot clinical trial have shown that blocking this pathway using a drug known as NBD peptide can promote cancerous cell death.
This clinical trial expands on our previous pilot study and aims to determine whether NBD peptide can
- inhibit aberrant pathway activity and kill cancer cells in dogs with B cell lymphoma
- improve short and long term outcomes in dogs with lymphoma.
Your dog is eligible to participate in this clinical trial if:
- it has been diagnosed with diffuse large B-cell lymphoma
- it is newly diagnosed or has not received chemotherapy for the treatment of lymphoma for at least 3 weeks
- it weighs less than 50kg
- it is otherwise healthy with no major organ disease
- it has evidence of an active NF-kappaB pathway within their malignant lymph node (to be determined at screening visit)
Your dog is not eligible to participate in this study if:
- it has T-cell lymphoma
- it does not have constitutively active NF-kappaB activity in their malignant lymph node
- it is systemically unwell
- There is no fee to participate in this study. All study procedures (including blood work and lymphoma immunophenotyping) plus study medication (NBD peptide and antibiotics) will be provided at no cost.
- The study will pay for a single dose of standard chemotherapy.
- The potential benefits could include increased responsiveness to chemotherapy leading to remission and prolonged remission times in patients receiving the NBD peptide.
Evaluation of a Recombinant Listeria Monocytogenes Vector Expressing huHer-2/neu to Stimulate Anti-tumor Immunity and Prolong Survival Times in Dogs With Appendicular Osteosarcoma
Osteosarcoma (bone cancer) is most commonly seen in large and giant breed dogs. It is an aggressive cancer with a guarded prognosis, even when treated with amputation and chemotherapy. The purpose of this study is to determine whether a recombinant L. moncytogenes vaccine can make the dog’s own immune system attack the tumor and prolong survival in dogs with appendicular osteosarcoma.
We are conducting a pilot phase I dose escalation study to determine the dose of a L. monocytogenes expressing huHer-2/neu recombinant vaccine that can effectively stimulate tumor-specific immunity and prolong survival in dogs with osteosarcoma. Only those dogs with a confirmed diagnosis of osteosarcoma (by biopsy) and who have undergone limb amputation and standard chemotherapy (four doses of carboplatin) for the treatment of osteosarcoma will be eligible for inclusion in the study. In addition, only those patients whose tumors express the target Her-2/neu will be eligible for inclusion in this study.
At enrollment (3 weeks following the last dose of carboplatin chemotherapy), all eligible dogs will receive basic clinical laboratory tests including a complete blood count, chemistry screen and urinalysis, and a baseline evaluation of cardiac function by echocardiography and measurement of cardiac-specific Troponin I (cTnI) levels. Chest X-rays will be taken to determine whether cancer has spread to the lungs (metastases). Only dogs with no evidence metastases will be eligible for inclusion in the study. At the time of enrollment, a blood sample will be taken to assess immune function and baseline levels of anti-tumor immunity.
All dogs will be vaccinated using a L. monocytogenes expressing huHer-2/neu recombinant vaccine; there is no placebo group. The first vaccine will be given 3 weeks after the last dose of routine carboplatin chemotherapy. Patients will receive a total of three vaccines given 3 weeks apart. Patients will stay in the hospital for 48 hours following vaccine administration for observation.
- Complete staging of disease at the time of enrollment (blood work, urinalysis, immune function assessment, chest X-rays, cardiac evaluation)
- Three Listeria monocytogenes vaccines
- Hospitalization for observation
- Blood work, urinalysis, and cardiac evaluation every 3 weeks for a total of 9 weeks
- Routine staging every 2 months following last vaccine administration (blood work, urinalysis, immune assessment, chest X-rays, cardiac evaluation)
- Four doses of carboplatin chemotherapy for dogs whose tumor expresses Her-2/neu (diagnosed after limb amputation)
There is no cost to participate in this study. Initial diagnosis, amputation, and related charges are not covered by the study.