Intra-tumoral administration of tumor membrane vesicles expressing GPI-anchored IL-2 inhibit tumor growth in a murine breast cancer model (P2080)

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Abstract Cancer is the second leading cause of death in the US with breast cancer being among the most common cancers. Tumor membrane vesicles (TMVs) used a vaccine will present a variety of tumor antigens to the immune system. TMVs due to their size and particulate nature are likely to be processed and presented by dendritic cells. To enhance their immunogenicity, TMVs were prepared from homogenized 4T07 mouse breast cancer cell transfectants expressing GPI-IL-2 Expression of GPI-IL-2 was verified by flow cytometry analysis. To ensure functionality, IL-2 expressing TMVs were co-cultured with CTLL-2 cells, an IL-2 dependent cytotoxic T cell line, for 48hrs and proliferation of the CTLL-2 cells was assessed by thymidine incorporation. Mice were then challenged with live wild-type 4T07 cells and administered 50ug of TMVs intra-tumorally on days 10 and 17 post tumor challenge. We observed that GPI-IL-2 expressing TMVs are functionally active and capable of inducing proliferation of CTLL-2 cells. More importantly, intra-tumoral injection of GPI-IL-2 expressing TMVs is capable of significantly reducing overall tumor burden in a therapeutic setting. These studies provide evidence that intra-tumoral vaccination with TMVs expressing GPI-IL-2 could potentially be a viable immunotherapeutic strategy for breast cancers that cannot be surgically removed.