Our laboratory research focuses on the study of tumor immunobiology and designing immunotherapies for the treatment of cancer. Our translational murine models and human in vitro studies are intended to serve as a foundation for the development of phase I/II clinical trials of modalities that can more effectively treat patients with melanoma or renal cell carcinoma. Such modalities include 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 (i.e., HSP90 inhibitors) or alter the balance of Type-1 versus regulatory immunity in the tumor microenvironment (i.e., sunitinib). Most recently, we have discovered that immune targeting of the tumor-associated vasculature occurs naturally as a consequence of effective immunotherapy (via DC1-based cross-priming of T cells), and that vaccines based on tumor-associated blood antigens (TBVA) can promote tumor regression even in cases where cancer cells cannot be directly recognized by the protective CD8+ immune system. We have also determined that anti-angiogenic agents such as the tyrosine kinase inhibitors sunitinib, axitinib and dasatinib all lead to tumor vascular normalization and to the improved delivery of anti-TBVA T cells into the tumor microenvironment (TME) allowing for improved anti-tumor efficacy. This has most recently resulted in the development of our NIH-supported clinical trial UPCI 12-048 'A Randomized Phase II Pilot Study of Type I-Polarized Autologous Dendritic Cell Vaccines Incorporating Tumor Blood Vessel Antigen (TBVA)-Derived Peptides in Combination with Dasatinib in Patients with Metastatic Melanoma' (H. Tawbi, Clinical PI) that is currently accruing patients.