Leukemia research reports · 2026
T cell dysfunction associated with repeated CAR-T cell manufacturing failure following prolonged bispecific antibody exposure: a case report.
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Henry Skylar J W, Pfeffer Kirsten, Shim Kevin G, Meermeier Erin W, Feng Fan, Wiedmeier Julia E, Chhabra Saurabh, Bergsagel P Leif, Fonseca Rafael, Wonnaparhown Alex M, Gustafson Michael P
Аннотация
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.
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.