PMID- 36612246
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230111
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 15
IP  - 1
DP  - 2022 Dec 30
TI  - Combination of Expanded Allogeneic NK Cells and T Cell-Based Immunotherapy Exert 
      Enhanced Antitumor Effects.
LID - 10.3390/cancers15010251 [doi]
LID - 251
AB  - Immunotherapies based on immune checkpoint blockade, neoantigen-reactive 
      tumor-infiltrating lymphocytes and T cell receptor-engineered T cells (TCR-T) 
      have achieved favorable clinical outcomes in tumor treatment. However, sustained 
      immune response and tumor regression have been observed only in a few patients 
      due to immune escape. Natural killer (NK) cells can mediate direct tumor lysis 
      and target cancer cells with low or no expression of human leukocyte antigen 
      class I (HLA-I) that are no longer recognized by T cells during immune escape. 
      Therefore, the combination of T cell-based immunotherapy and NK cell therapy is a 
      promising strategy for improving antitumor response and response rate. However, 
      allogeneic NK cells for adoptive cell therapy have been limited by both the 
      required cell number and quality. Here, we developed an efficient manufacturing 
      system that relies on genetically modified K562 cells for the expansion of 
      high-quality NK cells derived from peripheral blood mononuclear cells. NK cells 
      with the optimal expansion and activity were identified by comparing the 
      different culture systems. Furthermore, we demonstrated that the cooperation of 
      NK cells with tumor-reactive T cells or with NY-ESO-1-specific TCR-T cells 
      further enhanced tumors lysis, especially against tumors with downregulated HLA-I 
      expression. The advantages of HLA-mismatch and non-rejection by other allogeneic 
      immune cells demonstrated the potential of "off-the-shelf" NK cells with the 
      capacity to target tumors for immunotherapy. Our results indicate that the 
      combination strategy based on T cell and allogeneic NK cell immunotherapy might 
      have potential for overcoming the barrier of immune incompetence caused by HLA-I 
      downregulation.
FAU - Wang, Xiao
AU  - Wang X
AD  - Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, 
      National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
FAU - Yang, Xuejiao
AU  - Yang X
AD  - Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, 
      National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
FAU - Wang, Yueping
AU  - Wang Y
AD  - Institute of Interdisciplinary Sciences, Shanghai University of Traditional 
      Chinese Medicine, Shanghai 201203, China.
FAU - Chen, Yunshuo
AU  - Chen Y
AD  - Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, 
      National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
FAU - Yang, Ying
AU  - Yang Y
AD  - Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, 
      National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
FAU - Shang, Siqi
AU  - Shang S
AD  - Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, 
      National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
FAU - Wang, Wenbo
AU  - Wang W
AD  - Department of Oncology, Shanghai Tenth People's Hospital, Tongji University 
      School of Medicine, Shanghai 200072, China.
AD  - LeaLing Biopharma Company, Ltd., Suzhou 215000, China.
FAU - Wang, Yueying
AU  - Wang Y
AUID- ORCID: 0000-0002-8092-7775
AD  - Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, 
      National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, 
      Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
LA  - eng
GR  - 82270164/National Natural Science Foundation of China/
GR  - 20152507/Shanghai Municipal Education Commission/
PT  - Journal Article
DEP - 20221230
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC9818244
OTO - NOTNLM
OT  - T cell receptor-engineered T cells
OT  - combination immunotherapy
OT  - human leukocyte antigen
OT  - natural killer cells
OT  - tumor-reactive T cells
COIS- The authors declare no conflict of interest.
EDAT- 2023/01/09 06:00
MHDA- 2023/01/09 06:01
PMCR- 2022/12/30
CRDT- 2023/01/08 01:08
PHST- 2022/11/30 00:00 [received]
PHST- 2022/12/26 00:00 [revised]
PHST- 2022/12/27 00:00 [accepted]
PHST- 2023/01/08 01:08 [entrez]
PHST- 2023/01/09 06:00 [pubmed]
PHST- 2023/01/09 06:01 [medline]
PHST- 2022/12/30 00:00 [pmc-release]
AID - cancers15010251 [pii]
AID - cancers-15-00251 [pii]
AID - 10.3390/cancers15010251 [doi]
PST - epublish
SO  - Cancers (Basel). 2022 Dec 30;15(1):251. doi: 10.3390/cancers15010251.