Antibody‐dependent cell‐mediated cytotoxicity using T cells with NK‐like phenotype in combination with avelumab, an anti‐PD‐L1 antibody. Issue 2 (15th August 2022)

• Record Type: Journal Article
• Authors: Liu, Dong; Hu, Yuefeng; Wei, Jian; Zhang, Wen; Piao, Chunmei; Lu, Yongcheng; Wang, Yue; Liu, Jingwei; Lu, Xu
• Is Part Of: Immunology. Volume 167:Issue 2(2022)
• Page Start: 212
• Page End: 220
• Publication Date: 2022-08-15
• Subjects: adoptive cell‐based immunotherapy -- CD16 -- checkpoint inhibitor -- orthotopic xenograft; Immunology -- Periodicals
• DOI: 10.1111/imm.13530
• Languages: English
• ISSNs: 0019-2805

Abstract

Abstract: Though the PD‐L1 checkpoint inhibitor avelumab has shown efficacy in the treatment of some types of cancer, improved treatment strategies are desperately needed. We evaluated whether combined treatment with avelumab and adoptively transferred T‐NK cells can provide enhanced anti‐cancer effects for treating PD‐L1‐expressing tumours. Our results demonstrate that avelumab specifically targets tumour cells with high PD‐L1 expression, and that cytolytic effects are mediated by T‐NK effector cells cultured from patient peripheral blood monocytic cell populations. The effects were dependent on CD16 and the perforin/granzyme pathway, supporting a role for the T‐NK subpopulation. In vivo assays verified the efficacy of T‐NK cells in combination with avelumab in reducing tumour growth. Furthermore, T‐NK + avelumab prolonged survival in a mouse orthotopic xenograft model. Collectively, our findings provide a basis for the combined use of adoptively transferred T‐NK cells with avelumab as a novel strategy for cancer treatment. Abstract : This study provides important insights into the potential efficacy of combining adoptive transfer of T‐NK cells and anti‐PD‐L1 antibody (avelumab) as a novel strategy for cancer intervention, with notable application for solid tumors. In vitro assays using PBMCs from cancer patients demonstrated the specificity for high PD‐L1 expressing tumor cells and potency of antibody‐dependent cell‐mediated cytotoxicity (ADCC) of the combination treatment. Furthermore, in vivo assays using mouse orthotopic xenografts demonstrated reduced tumor growth and prolonged survival. Our results may inform new strategies for clinical intervention of cancer, including cancers that are not eligible for CAR‐T therapy.