Abstract A043: Safety and efficacy of a genetic vaccine targeting telomerase against various canine cancers

Abstract

Purpose of the study: we have recently shown that a genetic vaccine targeting dog telomerase (dTERT) and based on Ad (Adenovirus)/DNA-EP (DNA electroporation) technology can induce strong immune response and increase overall survival (OS) of dogs affected by B-cell malignant lymphoma (ML) when combined to COP therapy in a limited number of subjects. In this study, we have conducted a double arm clinical trial with an extended number of ML patients and evaluated the immunotherapy in dogs affected by other tumor types, such as mesothelioma, hemangiosarcoma, melanoma and renal cancer.

Methods: Dogs are vaccinated by a protocol consisting of 2Ad vector injections (Priming phase) and followed by DNA-EP (Boosting phase) by means of a Cliniporator device, currently utilized and approved in Europe for Electrochemotherapy applications and adapted to Electro-Gene-Transfer. The vaccine was combined with Standard of care (SOC) therapies. The immune response was measured by ELISPOT, Intracellular staining for cytokines and ELISA assays.

Results: No adverse effects were observed in any dog patient that could be attributed to treatment. dTERT-specific immune response was induced in almost all treated animals. The OS of vaccine/COP treated ML-dogs was significantly increased over contemporaneous COP-treated animals (>76.1 vs 29.3 weeks, respectively, p<0.0001). The evaluation of the OS for the other tumor types is in progress. The association of the therapeutic effects and vaccine potency with biomarkers such as T regulatory cells (Tregs) and Myeloid derived suppressor cells (MDSC) is also in progress.

Conclusions: Ad/DNA-EP-based cancer vaccine against dTERT in combination with COP chemotherapy is safe and significantly prolongs the survival of ML canine patients. These data confirm the therapeutic efficacy of dTERT vaccine and hold promise for the treatment of dogs affected by other cancer types. Most importantly, our study outlines the relevance of canine patients as relevant preclinical models for human cancer vaccines.

Citation Format: Joseph A. Impellizeri, Alessandra Gavazza, George Lubas, Eliana Greissworth, David Jemiolo, Gennaro Ciliberto, Luigi Aurisicchio. Safety and efficacy of a genetic vaccine targeting telomerase against various canine cancers. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A043.