Recently, immunotherapies have been demonstrated to induce complete remission in cancer patients. However, induction of long-term complete remission by these therapies is limited to a part of patients with some solid tumors including ovarian cancers. Therefore, there is a critical need to develop novel immunotherapeutic approaches which induce durable remission in a broad population of ovarian cancer patients. Our research in this project has focused on a novel subset of CD4+ “helper” T cells, which we discovered in ovarian cancer patients and named “tumor-recognizing CD4+ T cells (TR-CD4 cells)”. Our previous studies in human TR-CD4 cells have demonstrated that TR-CD4 cells not only inhibit tumor growth, but also strongly enhance and prolong antitumor activity of CD8+ “killer” T cells and B cells.
Therefore, utilization of TR-CD4 cells is a promising immunotherapeutic approach to induce potent and durable antitumor immunity in cancer patients. In this project, in order to develop immunotherapy based on TR-CD4 cells, we will develop vaccine therapy and adoptive cell therapy that efficiently induce TR-CD4 cells in murine ovarian tumor models. We expect that our experiments in this research will provide critical information regarding physiological induction and antitumor function of TR-CD4 cells. After successful completion of this study, we expect to further develop our novel immunotherapy utilizing TR-CD4 cells in clinical trials to improve outcome of ovarian cancer patients.
Dr. Takemasa Tsuji joined the faculty in 2013 as an Assistant Professor of Oncology in the Center for Immunotherapy at Roswell Park Comprehensive Cancer Center. His research goal is to develop potent immunotherapeutic strategies that induce life-long tumor remission in broad cancer patients. He received bachelor’s and master’s degrees in Science from Hirosaki University and PhD from Hokkaido University in JAPAN. After obtaining his PhD, he conducted laboratory research as a post-doctoral research fellow in the laboratories of Dr. Takashi Nishimura (Hokkaido University), Dr. Lloyd J. Old (Ludwig Institute for Cancer Institute/Memorial Sloan-Kettering Cancer Center, NY), and Dr. Kunle Odunsi (Roswell Park Comprehensive Cancer Center, NY). His research during post-doctoral training has been focused on understanding the mechanisms of immunologic recognition of human cancers such that specific immunotherapies can be applied on a personalized basis.
His research in the past few years has led to the identification and characterization of a unique CD4+ T cell subset, which is named “tumor-recognizing CD4+ helper T cell (TR-CD4 cell)”, that directly recognizes cancer cells. Through direct recognition of cancer cells, TR-CD4 cells significantly inhibit tumor cell growth and potently induce or augment anti-tumor functions of other immune-cell subsets. To develop novel immunotherapy against ovarian cancers utilizing TR-CD4 cells, he will conduct preclinical research with the support from the Ovarian Cancer Research Alliance, Liz Tilberis Award. Dr. Tsuji received Alliance Foundation Awards from Roswell-Park Alliance foundation. He has also been a co-investigator in a New York State Stem Cell Science (NYSTEM) grant.