Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a highly efficacious treatment modality for refractory and relapsed hematopoietic malignancies in recent years. Furthermore, CAR technologies for cancer immunotherapy have expanded from CAR-T to CAR-natural killer cell (CAR-NK), CAR-cytokine-induced killer cell (CAR-CIK), and CAR-macrophage (CAR-MΦ) therapy. Nevertheless, the high cost and complex manufacturing processes of ex vivo generation of autologous CAR products have hampered broader application. There is an urgent need to develop an efficient and economical paradigm shift for exploring new sourcing strategies and engineering approaches toward generating CAR-engineered immune cells to benefit cancer patients. Currently, researchers are actively investigating various strategies to optimize the preparation and sourcing of these potent immunotherapeutic agents. In this work, the latest research progress is summarized. Perspectives on the future of CAR-engineered immune cell manufacturing are provided, and the engineering approaches, and diverse sources used for their development are focused upon.
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http://dx.doi.org/10.1002/advs.202303215 | DOI Listing |
Cell Rep
January 2025
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address:
CD226 plays a vital role in natural killer (NK) cell cytotoxicity, interacting with its ligands CD112 and CD155 to initiate immune synapse formation, primarily through leukocyte function-associated-1 (LFA-1). Our study examined the role of CD226 in NK cell surveillance of acute myeloid leukemia (AML). NK cells in patients with AML had lower expression of CD226.
View Article and Find Full Text PDFCancer Cell Int
December 2024
Division of Cancer Biology, Laboratory Animal Center, The Fourth Military Medical University, Xi'an, 710032, Shaanxi, China.
Tumor organoids have emerged as powerful tools for in vitro cancer research due to their ability to retain the structural and genetic characteristics of tumors. Nevertheless, the absence of a complete tumor microenvironment (TME) limits the broader application of organoid models in immunological studies. Given the critical role of immune cells in tumor initiation and progression, the co-culture model of organoids and peripheral blood mononuclear cells (PBMCs) may provide an effective platform for simulating the interactions between immune and tumor cells in vitro.
View Article and Find Full Text PDFFront Immunol
December 2024
State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Background: Chimeric antigen receptor (CAR) engineered natural killer (NK) cells exhibit advantages such as MHC-independent recognition and strong anti-tumor functions. However, allogeneic CAR-NK cells derived from human tissues are heterogeneous and susceptible to clearance by hosts.
Methods: We generated a B2M knockout, HLA-E and CD19 CAR ectopic expressing embryonic stem cell (ESC) line, which differentiated normally and gave rise to homogeneous CD19 CAR-NK (CD19 CAR-UiNK) cells using an organoid aggregate induction method.
Exp Hematol Oncol
December 2024
Department of Pediatrics, Shengjing Hospital of China Medical University, No.36, Sanhao Street, Shenyang, 110004, Liaoning, China.
J Neurooncol
November 2024
Department of Neurological Surgery, Pauline Braathen Neurological Center, Cleveland Clinic Florida, Weston, FL, USA.
Glioblastoma (GBM) is a highly aggressive primary brain tumor that carries a grim prognosis. Because of the dearth of treatment options available for treatment of GBM, Chimeric Antigen Receptor (CAR)-engineered T cell and Natural Killer (NK) therapy could provide alternative strategies to address the challenges in GBM treatment. In these approaches, CAR T and NK cells are engineered for cancer-specific immunotherapy by recognizing surface antigens independently of major histocompatibility complex (MHC) molecules.
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