B7-H3 chimeric antigen receptor-modified T cell shows potential for targeted treatment of acute myeloid leukaemia

Eur J Med Res. 2023 Mar 20;28(1):129. doi: 10.1186/s40001-023-01049-y.

Abstract

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.

Keywords: Acute myeloid leukaemia; B7-H3; Chimeric antigen receptor-T cell; Immunotherapy.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cytokines / metabolism
  • Immunotherapy, Adoptive / methods
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / therapy
  • Mice
  • Receptors, Chimeric Antigen* / genetics
  • Receptors, Chimeric Antigen* / metabolism
  • T-Lymphocytes / metabolism

Substances

  • Receptors, Chimeric Antigen
  • Cytokines