ArticleImmunoTargets and therapy2026
Integrin alpha8beta1 is Identified as a Potential CAR-T Target for BCMA-Resistant Relapsed Multiple Myeloma.
Article in ImmunoTargets and therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: B cell maturation antigen (BCMA)-targeted chimeric antigen receptor T cell (CAR-T) therapy has improved outcomes for relapsed/refractory multiple myeloma (R/R MM), but most patients eventually relapse, largely due to antigen escape, clonal heterogeneity, and immune-evasive tumor subclones. Novel targets are urgently needed to complement BCMA CAR-T and reduce relapse. Methods: We analyzed several single-cell transcriptomic datasets from patients who relapsed after BCMA CAR-T to identify relapse-associated surface antigens. We characterized ITGA8 expression in normal tissues and hematopoietic cells, evaluated its biological function in myeloma cells, and generated α8β1-targeted CAR-T cells. Preclinical efficacy was assessed in vitro and in xenograft models in combination with BCMA CAR-T. Results: ITGA8 was significantly enriched in MM cells at early relapse following BCMA CAR-T therapy, marking a quiescent, immune-evasive subpopulation. ITGA8 was absent from normal hematopoietic stem and immune cells but showed restricted expression in vascular smooth muscle cells. α8β1 CAR-T specifically lysed ITGA8-positive myeloma cells and complemented with BCMA CAR-T to control tumor in models mimicking antigen loss. Conclusion: This preclinical proof-of-concept study identifies integrin α8β1 as a potential CAR-T target worthy of further development for BCMA-resistant relapsed MM. While short-term tumor control was improved, this does not equate to validated clinical relapse prevention. Safety related to off-tumor expression in non-hematopoietic tissues remains to be fully evaluated.
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