Unlocking the potential of allogeneic Vδ2 T cells for ovarian cancer therapy through CD16 biomarker selection and CAR/IL-15 engineering

Derek Lee, Zachary Spencer Dunn, Wenbin Guo, Carl J. Rosenthal, Natalie E. Penn, Yanqi Yu, Kuangyi Zhou, Zhe Li, Feiyang Ma, Miao Li, Tsun-Ching Song, Xinjian Cen, Yan-Ruide Li, Jin J. Zhou, Matteo Pellegrini, Pin Wang and Lili Yang ()
Additional contact information
Derek Lee: University of California
Zachary Spencer Dunn: University of California
Wenbin Guo: University of California
Carl J. Rosenthal: University of California
Natalie E. Penn: University of California
Yanqi Yu: University of California
Kuangyi Zhou: University of California
Zhe Li: University of California
Feiyang Ma: University of California
Miao Li: University of California
Tsun-Ching Song: University of California
Xinjian Cen: University of California
Yan-Ruide Li: University of California
Jin J. Zhou: University of California
Matteo Pellegrini: University of California
Pin Wang: University of Southern California
Lili Yang: University of California

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-42619-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42619-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-42619-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().