Antibody-dependent cell-mediated cytotoxicity using T cells with NK-like phenotype in combination with avelumab, an anti-PD-L1 antibody.

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.

• Authors: Dong Liu, Yuefeng Hu, Jian Wei, Wen Zhang, Chunmei Piao, Yongcheng Lu, Yue Wang, Jingwei Liu, Xu Lu
• Journal: Immunology (Immunology) Vol. 167 Issue 2 Pg. 212-220 (10 2022) ISSN: 1365-2567 [Electronic] England
• PMID: 35751879 (Publication Type: Journal Article)
• Copyright: © 2022 John Wiley & Sons Ltd.

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• B7-H1 Antigen
• Perforin
• Granzymes
• avelumab

Topics

• Animals
• Antibodies, Monoclonal (genetics, pharmacology, therapeutic use)
• Antibodies, Monoclonal, Humanized
• B7-H1 Antigen
• Cell Line, Tumor
• Granzymes (genetics)
• Humans
• Killer Cells, Natural
• Mice
• Perforin (genetics)
• Phenotype
• T-Lymphocytes (metabolism)