Background And Aims: Chimeric antigen receptor (CAR)-T cell therapy is a novel type of immunotherapy. However, the use of CAR-T cells to treat acute myeloid leukaemia (AML) has limitations. B7-H3 is expressed in several malignancies, including some types of AML cells. However, its expression in normal tissues is low. Therefore, B7-H3 is ideal for targeted AML therapy.
Materials And Methods: First, we constructed B7-H3 CAR that can target B7-H3, and then constructed B7-H3-CAR-T cells in vitro, which were co-incubated with six AML cell lines expressing different levels of B7-H3, respectively. The toxicity and cytokines were detected by flow cytometry. In vivo, AML model was established in B-NSG mice to study the toxicity of B7-H3-CAR T on AML cells.
Results: In vitro functional tests showed that B7-H3-CAR-T cells were cytotoxic to B7-H3-positive AML tumor cells and had good scavenging effect on B7-H3-expressing AML cell lines, and the cytokine results were consistent. In vivo, B7-H3-CAR-T cells significantly inhibited tumor cell growth in a mouse model of AML, prolonging mouse survival compared with controls.
Conclusion: B7-H3-CAR-T cells may serve as a novel therapeutic method for the targeted treatment of AML.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10026503 | PMC |
http://dx.doi.org/10.1186/s40001-023-01049-y | DOI Listing |
Clin Transl Oncol
November 2024
Institute of Clinical Medicine, the Second Affiliated Hospital of Hainan Medical University, 368 Yehai Avenue, Haikou, 570311, Hainan, China.
Mol Immunol
December 2024
Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Center of Clinical Oncology, the Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221002, China; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China. Electronic address:
Cancer Immunol Immunother
October 2024
World Premier International Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan.
J Clin Oncol
December 2024
Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, WA.
Clin Cancer Res
October 2024
Department of Bone Marrow Transplantation and Cell Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee.
Purpose: Clinical efficacy of chimeric antigen receptor (CAR) T cells against pediatric osteosarcoma (OS) has been limited. One strategy to improve efficacy may be to drive chemokine-mediated homing of CAR T cells to tumors. We sought to determine the primary chemokines secreted by OS and evaluate the efficacy of B7-H3.
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