학술논문
Antibody‐dependent cell‐mediated cytotoxicity using T cells with NK‐like phenotype in combination with avelumab, an anti‐PD‐L1 antibody.
Document Type
Article
Author
Source
Subject
*ANTIBODY-dependent cell cytotoxicity
*T cells
*GRANZYMES
*PERFORINS
*CELL populations
*BLOOD cells
*IMMUNOGLOBULINS
*
*
*
*
*
*
Language
ISSN
0019-2805
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 FROM AUTHOR]