Comparing the efficacy of combined versus single immune cell adaptive therapy targeting colorectal cancer

作者：Denis Nchang, NaHye Lee, Hyo-Jung Lee, Y.M. Kim, Solongo Battulga, Ha Na Lee, W.S. Ham, Hyunah Lee, Mi Young Lee, D.Y. Kim, Haengji Kang, Subin Yun, Jinju Park, Daeyoun David Won, Jong Kyun Lee · 发表于：Annals of Coloproctology · 年份：2024 · DOI：10.3393/ac.2023.00402.0057 · 研究领域：CAR-T cell therapy research、Immune Cell Function and Interaction、Immunotherapy and Immune Responses

PURPOSE: Colorectal cancer (CRC) is the most frequent cancer with limited therapeutic achievements. Recently, adoptive cellular immunotherapy has been developed as an antitumor therapy. However, its efficacy has not been tested in CRC. This study investigated the ability of an immune cell cocktail of dendritic cells (DCs), T cells, and natural killer (NK) cells to overcome immunological hurdles and improve the therapeutic efficacy of cell therapy for CRC. METHODS: CRC lysate-pulsed monocyte-derived DCs (Mo-DCs), CRC antigen-specifically expanded T cells (CTL), and in vitro-expanded NK cells were cultured from patient peripheral blood mononuclear cells (PBMC). The ability of the combined immune cells to kill autologous tumor cells was investigated by co-culturing the combined immune cells with patient-derived tumor cells. RESULTS: The Mo-DCs produced expressed T cell co-stimulating molecules like CD80, CD86, human leukocyte antigen (HLA)-DR and HLA-ABC, at high levels and were capable of activating naive T cells. The expanded T cells were predominantly CD8 T cells with high levels of CD8 effector memory cells and low levels of regulatory T cells. The NK cells expressed high levels of activating receptors and were capable of killing other cancer cell lines (K562 and HT29). The immune cell cocktail demonstrated a higher ability to kill autologous tumor cells than single types. An in vivo preclinical study confirmed the safety of the combined immune cell adaptive therapy showing ...