In situ vaccine for low-grade lymphoma: Combination of intratumoral Flt3L and poly-ICLC with low-Dose radiotherapy.

TPS3105 Background: Lymphomas are the 5th most incident cancer in the U.S. and indolent non-Hodgkin's lymphoma (iNHL) are incurable with standard therapy. We previously completed three trials of ‘in situ vaccination’ - combining low-dose radiotherapy (XRT) with intratumoral administration of a TLR9 agonist (CpG). We demonstrated induction of tumor-specific CD8 T cell responses and clinical remissions of patients’ untreated sites of disease, lasting up to > 4 years. One limitation may have been the scarcity of intratumoral dendritic cells (DC). DC are uniquely able to endocytose dying (e.g. irradiated) tumor cells for cross-presentation to anti-tumor CD8 T cells. Methods: Flt3L– the predominant DC differentiation factor– induces tumor leukocyte infiltration and regression of lymphoma tumors pre-clinically and a new formulation of this cytokine -CDX-301- was shown to mobilize BDCA-1 and BDCA-3 DC subsets in an early phase trial. These DC subsets respond to several TLR agonists and cross-present antigens mor...