Increasing evidence has shown that macrophage infiltrates and accumulates at specific "niches" of tumor tissue and plays a significant role for tumor growth and metastasis. The cytokine milieu in tumor drives macrophages to express polarized functions (M1 and M2 paradigm). M2-polarized tumor-associated macrophages (M2-TAMs) have been shown to promote angiogenesis, mediate immune suppression and inhibit the development of innate and adaptive immunity, thus, exert tumor-promoting activity and correlate with poor prognosis and survival. M2-TAMs are considered to be one of the major factors in tumor microenvironment that limit the efficacy of cancer therapies including chemotherapies, cellular immunotherapies, and other therapies in clinical trials. For past years, we have focused our research on the development of nanotechnology that can specifically target, image, assess and manipulate M2-TAMs in tumor microenvironment. We aim to use innovative nanomedicine to establish in vivo environment that is favorable for patients to develop tumor destructive immune responses.
We currently have a phae I clinical trial of adoptive immunotherapy for Stage III/IV melanoma patients (led by Dr. Julian Kim, Division of Surgical Oncology). In this trial, we aim to develop ex vivo-expanded melanoma-specific stem-like CD4 positive T cells from melanoma draining lymph node, which anticipates to mediating durable immune responses upon adoptive administration.
Since strong immune suppression has been demonstrated to limit the efficacy of adoptive cellular immunotherapy, the ultimate goal of our research is to combine nanomedicine, TAM-targeted therapy and T cell therapy to develop innovative immunotherapeutic strategy for cancer.