Fig. 5.

Other kind of cell therapy. a Preparation of CAR-NK and the mechanisms of CAR-NK cell. The preparation of CAR-NK cells involves isolating NK cells from sources such as umbilical cord blood or hematopoietic stem cells, followed by genetic modification to integrate a CAR construct that includes an antigen recognition domain. These cells are then expanded in vitro before being infused back into the patient. Once in the body, CAR-NK cells utilize their CAR to recognize and bind to specific tumor antigens, leading to their activation and the subsequent release of cytotoxic granules and cytokines to eliminate cancer cells. Additionally, the Fc receptor CD16 on NK cells can mediate ADCC, further enhancing their tumoricidal activity. b Preparation of TIL. The preparation of tumor-infiltrating lymphocytes (TIL) involves isolating immune cells from a patient’s tumor tissue, where they have naturally infiltrated. The process typically includes surgical removal of the tumor mass, followed by the mechanical and enzymatic dissociation of the tissue to obtain a single-cell suspension. The cells are then cultured in vitro, and the TILs, which are often CD8+ T cells, are selectively expanded through various techniques, such as interleukin-2 (IL-2) stimulation. Once a sufficient number of TILs are obtained, they are infused back into the patient as part of the adoptive cell transfer therapy, aiming to boost the immune system’s ability to target and destroy cancer cells. c The structure comparation between TCR-T and CAR-T. TCR-T cells are genetically modified to express a specific T-cell receptor that recognizes MHC-presented antigens, allowing them to target a broad range of tumor-associated antigens, including those derived from intracellular proteins. In contrast, CAR-T cells are engineered to express a chimeric antigen receptor that includes an antibody-derived antigen-binding domain, enabling them to target cell surface antigens without MHC restriction. d The overview of CAR-M (workflow and generation). Once inside the patient’s body, the CAR-M cells use their CAR to identify and attach to tumor cells, which triggers the activation of the macrophages, leading to the subsequent engulfment and destruction of the tumor cells. Additionally, they secrete pro-inflammatory cytokines that recruit other cells from the immune microenvironment to join in the attack against the tumor. CAR-Ms are differentiated into first and second generations. The second generation includes an extra CD3 domain compared to the first, endowing it with enhanced pro-inflammatory properties and sustained M1 macrophage activation. This figure was created with Biorender.com