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

Tytuł:: Antibody-dependent cell-mediated cytotoxicity using T cells with NK-like phenotype in combination with avelumab, an anti-PD-L1 antibody.
Autorzy:: Liu D; Department of Radiology, The First Hospital of Tsinghua University, Beijing, China.
Hu Y; Department of Interventional Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Wei J; Department of Interventional Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Zhang W; Department of Oncology, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Piao C; Department of Oncology, Beijing Anzhen Hospital Affiliated to the Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
Lu Y; Department of Pharmaceutical Sciences, Bouvé College of Health Sciences, Northeastern University, Boston, Massachusetts, USA.
Wang Y; Department of Oncology, Beijing Biohealthcare Biotechnology Co., Ltd, Bejing, China.
Liu J; Department of Oncology, Beijing Biohealthcare Biotechnology Co., Ltd, Bejing, China.
Lu X; Department of Oncology, Beijing Biohealthcare Biotechnology Co., Ltd, Bejing, China.
Źródło:: Immunology [Immunology] 2022 Oct; Vol. 167 (2), pp. 212-220. Date of Electronic Publication: 2022 Aug 15.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Original Publication: Oxford : Blackwell Scientific Publications
MeSH Terms:: Antibodies, Monoclonal*/genetics
Antibodies, Monoclonal*/pharmacology
Antibodies, Monoclonal*/therapeutic use
T-Lymphocytes*/metabolism
Animals ; Antibodies, Monoclonal, Humanized ; B7-H1 Antigen ; Cell Line, Tumor ; Granzymes/genetics ; Humans ; Killer Cells, Natural ; Mice ; Perforin/genetics ; Phenotype
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Contributed Indexing:: Keywords: CD16; adoptive cell-based immunotherapy; checkpoint inhibitor; orthotopic xenograft
Substance Nomenclature:: 0 (Antibodies, Monoclonal)
0 (Antibodies, Monoclonal, Humanized)
0 (B7-H1 Antigen)
126465-35-8 (Perforin)
EC 3.4.21.- (Granzymes)
KXG2PJ551I (avelumab)
Entry Date(s):: Date Created: 20220625 Date Completed: 20220929 Latest Revision: 20221031
Update Code:: 20240105
DOI:: 10.1111/imm.13530
PMID:: 35751879
: Czasopismo naukowe

Pełny tekst

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.
(© 2022 John Wiley & Sons Ltd.)

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