Walter J. Storkus, PhD

Our laboratory studies tumor immunobiology and designs immunotherapies for the treatment of cancer based results gained in translational murine models and human in vitro studies, with the near-term goal of developing novel phase I/II clinical trials for the treatment of patients with melanoma. Such modalities have included dendritic cell (DC)-based vaccines, cytokine gene-modified DC injected directly into tumor lesions and combinational approaches integrating agents that modulate tumor cell immune recognition or alter the balance or Type-1 versus regulatory immunity in the tumor microenvironment. We have recently discovered that immune targeting of the tumor-associated vasculature occurs naturally during effective immunotherapy (via DC1-based cross-priming of T cells), and that vaccines based on tumor-associated blood vessel antigens (TBVA) promote tumor regression even in cases where cancer cells cannot be directly recognized by T cells. We have also determined that treatment with anti-angiogenic agents such as sunitinib, axitinib, dasatinib and STING agonists all lead to tumor vascular normalization and improved delivery of anti-TBVA T cells into the melanoma microenvironment (TME). Such inflammatory infiltrates may also sponsor the development of tertiary lymphoid structures (TLS), believed to serve as sites for “spreading” in the therapeutic anti-tumor T cell repertoire. We have translated a combined vaccine + dasatinib treatment design into a pilot phase II clinical trial (UPCI 12-048), where objective clinical responses were observed in approximately 40% of evaluable patients with advanced-stage cutaneous or uveal melanoma. Prospective clinical trials will integrate immune checkpoint blockade and extend treatment to patients with alternate forms of solid cancer.