CXCR4-modification enhances CAR-T efficacy by improving tumor tracking and bone marrow homing in B-cell malignancies.

ABSTRACT: Hematological malignancies of B cell origin are characterized by frequent expression of CXCR4. The CXCR4-CXCL12 axis facilitates the in vivo dissemination of B cell lymphoma and multiple myeloma (MM). It is also a pivotal regulator in the migration and bone marrow homing of T cells. Herein, we hypothesized that engineering CAR-T cells to overexpress CXCR4 could utilize the CXCR4-CXCL12 axis to enhance their therapeutic efficacy by increasing tumor tracking and bone marrow accumulation. In this study, we found that lentiviral transduction caused significant CXCR4 downregulation on T cells, leading to impaired CAR-T cell migration to CXCL12. By contrast, CXCR4 overexpressing (CXCR4^hi) CD19 CAR-T cells and BCMA CAR-T cells showed superior in vivo tumor tracking and clearance capaci

SUBMITTER: Shu P 

PROVIDER: S-EPMC12852854 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature