IMMU-41. RNA-MODIFIED T CELLS AS PROFESSIONAL ANTIGEN PRESENTING CELLS

Abstract INTRODUCTION With the lack of antigen presenting cells (APCs) in the central nervous system (CNS), anti-tumor immune responses from intracranial tumors are believed to be initiated in the peripheral lymph nodes. Recently, studies have shown that intratumoral dendritic cells (DCs), a well-known professional APC, play a crucial role at inducing anti-tumor immunity. Although DCs have been tested in cancer immunotherapy clinical trials for two decades, DC delivery strategies have limited access to the CNS, mainly due to the blood brain barrier (BBB). To bypass the limitations of the lack of intracranial APCs, we investigate the HYPOTHESIS that RNA-modified T cells can express and cross-present single tumor antigens locally within the CNS tumor microenvironment. Since activated T cells have an inherent ability to cross the BBB and can be genetically modified, this strategy makes them an attractive professional antigen presenting cells for cancer cell therapy. METHODS Using electroporation to deliver messenger RNA (mRNA) encoding a model tumor antigen to T cells, we evaluated the expression and cross-presentation capability of RNA-modified T cells. RESULTS We demonstrated that activated T cells can be genetically modified to express tumor antigens in vitro while retaining their inherent effector functions. Compared to unmodified T cells, T cells modified with tumor antigen encoding RNA showed high expression of inflammatory cytokines, including IFN gamma and TNF alpha and enhanced cellular proliferation and IL-2 secretion. Tumor antigen RNA-modified T cells demonstrated potent antigen presentation in vitro and importantly were significantly superior to RNA-loaded DCs in antigen presenting capacity. CONCLUSIONS This study strongly supports the implementation of a non-invasive and efficacious strategy to deliver “APC-like” T cell locally to brain tumors, thereby bypassing the lack of APCs within CNS malignancies.