ArticleLeukemia research reports2026
T cell dysfunction associated with repeated CAR-T cell manufacturing failure following prolonged bispecific antibody exposure: a case report.
Article in Leukemia research reports, 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
Overview: We describe a patient with two consecutive manufacturing failures after prolonged bispecific antibody treatment in which longitudinal immune phenotyping and functional assays were performed to investigate potential mechanisms. Background: CAR-T cell therapy and bispecific antibodies (BsAb) have significantly improved outcomes in relapsed/refractory multiple myeloma (r/rMM), yet the optimal treatment sequence remains unclear, particularly regarding the impact of prior BsAb exposure on downstream CAR-T manufacturability. Case Presentation: A 72-year-old man with r/rMM had two CAR-T cell manufacturing failure events following multiple therapies including an FcRL5 × CD3 bispecific antibody. Both collections yielded an insufficient CAR-T cell dose. Longitudinal immune phenotyping revealed markers of T cell dysfunction, including loss of CCR7, CD27, and CD28, alongside severely impaired TCR-driven proliferation with preserved interleukin-2 responsiveness. Conclusion: These findings link profound T cell dysfunction with repeated CAR-T cell manufacturing failures and suggest that pre-leukapheresis immune phenotyping may identify patients at risk for manufacturing failure.
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