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Regulatory T cells hamper the efficacy of T-cell-engaging bispecific antibody therapy.
Casey, Mika; Lee, Carol; Kwok, Wing Yu; Law, Soi Cheng; Corvino, Dillon; Gandhi, Maher K; Harrison, Simon J; Nakamura, Kyohei.
Afiliación
  • Casey M; Immune Targeting in Blood Cancers Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD.
  • Lee C; Immune Targeting in Blood Cancers Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD.
  • Kwok WY; Immune Targeting in Blood Cancers Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD.
  • Law SC; Mater Research, University of Queensland, Brisbane, QLD.
  • Corvino D; Institute of Experimental Oncology, University Hospital Bonn, Bonn.
  • Gandhi MK; Mater Research, University of Queensland, Brisbane, QLD.
  • Harrison SJ; Department of Clinical Haematology, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Melbourne, VIC, Australia; Sir Peter MacCallum, Department of Oncology, University of Melbourne, Parkville.
  • Nakamura K; Immune Targeting in Blood Cancers Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD. kyohei.nakamura@qimrberghofer.edu.au.
Haematologica ; 109(3): 787-798, 2024 Mar 01.
Article en En | MEDLINE | ID: mdl-37767564
T-cell-engaging bispecific antibodies (T-BsAb) have produced impressive clinical responses in patients with relapsed/refractory B-cell malignancies, although treatment failure remains a major clinical challenge. Growing evidence suggests that a complex interplay between immune cells and tumor cells is implicated in the mechanism of action and therefore, understanding immune regulatory mechanisms might provide a clue for how to improve the efficacy of T-BsAb therapy. Here, we investigated the functional impact of regulatory T (Treg) cells on anti-tumor immunity elicited by T-BsAb therapy. In a preclinical model of myeloma, the activation and expansion of Treg cells in the bone marrow were observed in response to anti-B-cell maturation antigen (BCMA) T-BsAb therapy. T-BsAb triggered the generation of induced Treg cells from human conventional CD4 cells after co-culture with tumor cells. Moreover, T-BsAb directly activated freshly isolated circulating Treg cells, leading to the production of interleukin-10 and inhibition of T-BsAb-mediated CD8 T-cell responses. The activation of Treg cells was also seen in bone marrow samples from myeloma patients after ex vivo treatment with T-BsAb, further supporting that T-BsAb have an impact on Treg homeostasis. Importantly, transient ablation of Treg cells in combination with T-BsAb therapy dramatically improved effector lymphocyte activities and disease control in the preclinical myeloma model, leading to prolonged survival. Together, this information suggests that therapy-induced activation of Treg cells critically regulates anti-tumor immunity elicited by T-BsAb therapy, with important implications for improving the efficacy of such treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticuerpos Biespecíficos / Mieloma Múltiple Límite: Humans Idioma: En Revista: Haematologica Año: 2024 Tipo del documento: Article Pais de publicación: Italia
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticuerpos Biespecíficos / Mieloma Múltiple Límite: Humans Idioma: En Revista: Haematologica Año: 2024 Tipo del documento: Article Pais de publicación: Italia