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Unlocking the potential of allogeneic Vδ2 T cells for ovarian cancer therapy through CD16 biomarker selection and CAR/IL-15 engineering.
Lee, Derek; Dunn, Zachary Spencer; Guo, Wenbin; Rosenthal, Carl J; Penn, Natalie E; Yu, Yanqi; Zhou, Kuangyi; Li, Zhe; Ma, Feiyang; Li, Miao; Song, Tsun-Ching; Cen, Xinjian; Li, Yan-Ruide; Zhou, Jin J; Pellegrini, Matteo; Wang, Pin; Yang, Lili.
Afiliação
  • Lee D; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Dunn ZS; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Guo W; Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA, USA.
  • Rosenthal CJ; Bioinformatics Interdepartmental Program, University of California, Los Angeles, CA, USA.
  • Penn NE; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Yu Y; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Zhou K; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Li Z; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Ma F; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Li M; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA, USA.
  • Song TC; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Cen X; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Li YR; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Zhou JJ; Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, CA, USA.
  • Pellegrini M; Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA, USA.
  • Wang P; Bioinformatics Interdepartmental Program, University of California, Los Angeles, CA, USA.
  • Yang L; Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, CA, USA.
Nat Commun ; 14(1): 6942, 2023 11 08.
Article em En | MEDLINE | ID: mdl-37938576
ABSTRACT
Allogeneic Vγ9Vδ2 (Vδ2) T cells have emerged as attractive candidates for developing cancer therapy due to their established safety in allogeneic contexts and inherent tumor-fighting capabilities. Nonetheless, the limited clinical success of Vδ2 T cell-based treatments may be attributed to donor variability, short-lived persistence, and tumor immune evasion. To address these constraints, we engineer Vδ2 T cells with enhanced attributes. By employing CD16 as a donor selection biomarker, we harness Vδ2 T cells characterized by heightened cytotoxicity and potent antibody-dependent cell-mediated cytotoxicity (ADCC) functionality. RNA sequencing analysis supports the augmented effector potential of Vδ2 T cells derived from CD16 high (CD16Hi) donors. Substantial enhancements are further achieved through CAR and IL-15 engineering methodologies. Preclinical investigations in two ovarian cancer models substantiate the effectiveness and safety of engineered CD16Hi Vδ2 T cells. These cells target tumors through multiple mechanisms, exhibit sustained in vivo persistence, and do not elicit graft-versus-host disease. These findings underscore the promise of engineered CD16Hi Vδ2 T cells as a viable therapeutic option for cancer treatment.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Transplante de Células-Tronco Hematopoéticas Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Ovarianas / Transplante de Células-Tronco Hematopoéticas Idioma: En Ano de publicação: 2023 Tipo de documento: Article