The overall goal of my research is to advance the integration of immunotherapy within comprehensive cancer care, as a complementary modality to surgery, chemo and radiotherapy. My group develops new methods of using ex vivo-educated dendritic cells, DC-activated T cells, combinatorial adjuvants and checkpoint blockers, to promote selectively accumulation of type-1 immune cells (CTLs, Th1 and NK cells) in tumor lesions, without amplifying pre-existing Treg- and MDSC responses, in order to enhance local immune surveillance and enhance overall therapeutic outcomes. Our current projects include: Development and clinical evaluation of therapeutic vaccines involving different subsets of “polarized” DCs (colorectal cancer, ovarian cancer, prostate cancer, melanoma, hematologic malignancies) Development and clinical evaluation of adoptive T cell therapies (ACT) using ex vivo-induced polyclonal CTLs (ovarian- & colorectal cancers and melanoma) Development and clinical evaluation of combinatorial approaches to enhance the effectiveness of vaccines, ACT and checkpoint blockers, but reprogramming tumor microenvironments for enhanced CTL infiltration and modulating intratumoral expression of PD-L1, PD-L2 and other checkpoints (colorectal cancer, ovarian cancer, prostate cancer, melanoma, bladder cancer, HPV-associated cancers) Development of combinatorial adjuvants to modulate DC functions in situ Counteracting cancer-related immunosuppressive mechanisms and their use in transplantation and autoimmunity Role of the immune system in the effectiveness of oncolytic virotherapies Role of the immune system in the effectiveness of chemotherapy and radiotherapy of cancer Interplay between psychologic stress and cancer immunity These interdisciplinary projects involving multiple clinical and laboratory teams, have been advanced as parts of the as multiple NIH-, DOD-, pharma and biotech-funded grants and program projects (single- and multi-institution P01s and P50/SPOREs; where I have been serving as the overall PI, overall co-PI or a Project Leader) and focusing on the therapy of melanoma, colon cancer, prostate cancer, ovarian cancer, and hematologic malignancies. Our current work includes phase I/II and phase II clinical testing of the resulting paradigms and methods in cancer patients, and development of similar treatments for patients with premalignant lesions and chronic infections resistant to standard forms of treatment.