Flt3L-based in situ vaccination for the treatment of lymphoma.

e19040Background: Low-grade B-cell lymphomas are generally incurable, with standard therapies inducing only temporary remissions. Tumor-targeted vaccines represent promising, novel treatment strategies. In a pre-clinical mouse model, we attempt to develop and optimize an in situ vaccine combining recruitment of dendritic cells (DC) and low-dose local radiotherapy (XRT) with intratumoral (i.t) administration of a toll-like receptor (TLR) agonist. Methods: A20 lymphoma-bearing mice were injected i.t. with Flt3L for 9 days, followed by local XRT (9Gy) and i.t. poly-ICLC for 5 days. Tumors, lymph nodes, and spleens were analyzed by flow cytometry and animals were monitored for tumor growth and survival. Results: Injection of Flt3L induced potent accumulation of DC at the tumor site, tumor-draining lymph node (TDLN) and the spleen, with intratumoral injection being superior to systemic injection in increasing intratumoral and TDLN DCs (Figure 1B). Local XRT increased the amount of mCherry+ DC in the tumor, ind...