442-P Characterizing human Vδ1+ and Vδ2+ γδ T cells for tumor immunotherapy development

• Published in: Journal for immunotherapy of cancer 2023-11, Vol.11 (Suppl 2), p.A1800-A1800
• Main Authors: Chan, Kok Fei, Li, Tianming, Ostrouska, Simone, Hammet, Andrew, Rigau, Marc, Uldrich, Adam P, Behren, Andreas
• Format: Article
• Language: English
• Subjects: Cancer therapies; Cytotoxicity; Immunotherapy; Lymphocytes; Regular Abstracts – Part 2; Tumors
• ISSN: 2051-1426
• DOI: 10.1136/jitc-2023-SITC2023.0442-P

BackgroundImmunotherapy has revolutionized the treatment of cancer, and has been instated as a ‘pillar’ of modern cancer treatments alongside chemotherapy, radiotherapy and surgery. Most tumor immunotherapy developments to date have focused on cytotoxic CD8+ T cells. Increasingly, γδ T cells are being considered as the next-generation tumor immunotherapy against difficult to treat solid tumors due to their potent cytotoxic and cytolytic functions, and natural tropism for the tumor microenvironment. Moreover, γδ T cells can recognize a broad range of tumors and infected cells without the requirement of antigen presentation via major histocompatibility complex (MHC) molecules. Previous studies have shown that a high number of γδ T cells within tumors is strongly correlated with overall patient survival across 25 cancer types.MethodsWe have isolated and expanded human Vδ1+ and Vδ2+ T cells and performed in vitro T cell killing assay. In vitro isolated human Vδ2+ T cells were used for adoptive cell transfer in tumor-bearing NSG mice.ResultsIn our hands, we show that human Vδ1+ and Vδ2+ T cell constitute only 0.05 to 0.62% and 0.34 to 3.02%, respectively of total circulating T cells. We are now routinely isolating and expanding human Vδ1+ and Vδ2+ T cells and have immunophenotyped and validated their capability to kill different types of tumor cells in vitro. Additionally, we show that in vitro isolated human Vδ2+ T cells can slow tumor growth in vivo and prolong the survival of tumor-bearing NSG mice when adoptively transferred.ConclusionsCollectively, our data showed that human γδ T cells are promising targets for tumor immunotherapy development.Ethics Approval‘This study was approved by Australian Red Cross for the isolation of human Vδ2+ γδ T cells from healthy donors’ peripheral blood mononuclear cells, agreement number: 21-07VIC-09.’‘This study was approved by Austin Health Animal Ethics Committee for adoptive cell transfer of human Vδ2+ γδ T cells into NSG mice, AEC Reference number: A2020/05661.’