CSPG4-specific immunity and survival prolongation in dogs with oral malignant melanoma immunized with human CSPG4 DNA.

PURPOSE: Due to the many similarities with its human counterpart, canine malignant melanoma (cMM) is a valuable model in which to assess the efficacy of novel therapeutic strategies. The model is herein used to evaluate the immunogenicity, safety, and therapeutic efficacy of a human chondroitin sulfate proteoglycan-4 (hCSPG4) DNA-based vaccine. The fact that homology between hCSPG4 and cCSPG4 amino-acidic sequences stands at more than 80% provides the rationale for using an hCSPG4 DNA vaccine in the cMM model. EXPERIMENTAL DESIGN: Dogs with stage II-III surgically resected CSPG4-positive oral MM were subjected to monthly intramuscular plasmid administration, which was followed immediately by electroporation (electrovaccination) for at least 6, and up to 20, months. The immunogenicity, safety, and therapeutic efficacy of the vaccine have been evaluated. RESULTS: hCSPG4 electrovaccination caused no clinically relevant local or systemic side effects and resulted in significantly longer overall and disease-free survival times in 14 vaccinated dogs as compared with 13 nonvaccinated controls. All vaccinated dogs developed antibodies against both hCSPG4 and cCSPG4. Seven vaccinated dogs were also tested for a cCSPG4-specific T-cell response and only two gave a detectable interferon (IFN)γ response. CONCLUSION: Xenogeneic electrovaccination against CSPG4 is able to overcome host unresponsiveness to the "self" antigen and seems to be effective in treating cMM, laying the foundation for its translation to a human clinical setting.

Transanal pull-through rectal amputation for treatment of colorectal carcinoma in 11 dogs.

OBJECTIVE: To evaluate outcome after transanal rectal pull-through amputation of single colorectal adenocarcinoma and in situ carcinoma (Tis) in dogs. STUDY DESIGN: Retrospective case series. ANIMALS: Dogs (n=11) with colorectal cancer. METHODS: Full-thickness colorectal amputation by either simple transanal (7 dogs) or combined abdominal-transanal (4) pull-through technique. RESULTS: Adenocarcinoma (8) and Tis (2) were removed with 3-6 cm of grossly normal tissue, cranial and caudal to the tumor, or in 1 Tis with 2 cm grossly normal tissue, cranial and caudal. Two dogs that had a combined abdominal-transanal approach died within 4 days. In the other dogs, postoperative complications included short-term tenesmus (6 dogs), rectal bleeding (11), rectal stricture (3), and long-term fecal incontinence (1). Postoperative recurrence and metastatic rates for adenocarcinoma were 18.2% and 0%, respectively. Median disease-free interval and survival time were not reached. Mean disease-free and overall survival times were 44.3 and 44.6 months (range, 0-75 months), respectively. CONCLUSION: En bloc excision of colorectal Tis and adenocarcinoma may be followed by a long survival. Complications of the transanal approach are usually moderate and self-limiting, but complications are more common and severe when more extensive resections are performed through a combined abdominal-transanal approach. CLINICAL RELEVANCE: Transanal rectal pull-through amputation is suitable for en bloc resection of colorectal neoplasia. A combined abdominal-transanal approach should be reserved for tumors extending from the mid-cranial region of the rectum to the descending colon.