Abstract 4766: Multivalent VRP-based anti-tumor immunotherapy is an effective therapeutic strategy in a rat model of breast cancer

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC It is widely accepted that the genetic instability of a tumor results in both intra- and inter-tumoral genetic heterogeneity, which leads to heterogeneous tumor-associated antigen (TAA) expression and contributes to the outgrowth of antigen-loss variants in response to immunologic selective pressure. Using a rat neu encoding, alphavirus based virus-like replicon particle (VRP) with restricted in vivo tropism for dendritic cells in a fully tolerant Fisher 344 rat mammary tumor (13762 MAT B III) model, we previously demonstrated the ability to cure a modest proportion, 20-40%, of rats with pre-existing mammary tumors and observed the outgrowth of antigen loss variant tumors in a proportion of animals that ultimately succumbed to their tumor. Thus, we hypothesized that strategies targeting multiple tumor antigens would lead to improved treatment efficacy. Expression of the cancer testes antigen, Brother of Regulator of Imprinted Sites (BORIS) was confirmed in the 13762 MAT B III tumor. Rats with pre-existing tumors were treated with VRP encoding either the TAA rat neu or the BORIS target antigen, alone or in combination. We found that targeting either rat neu or BORIS alone was effective in treating a proportion of animals. Interestingly, administration of both VRP agents at a single anatomic site drastically decreased the treatment efficacy, by approximately 50%, while separating their administration into two separate anatomic sites enhanced the treatment efficacy over that provided by each agent alone, to >56% cure rate. Herein, we will present data addressing potential mechanisms for these treatment observations. To our knowledge, this is the first report of multivalent anti-tumor immunotherapy utilizing solely the VRP vector system. These data represent an exceptionally promising platform upon which to build more efficacious immunotherapeutic strategies including those targeting multiple defined TAAs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4766.