Development of adoptive immunotherapy with KK-LC-1-specific TCR-transduced γδT cells against lung cancer cells.
Animals
Antigens, Neoplasm
/ immunology
Cell Line, Tumor
Cytokines
/ metabolism
Disease Models, Animal
Humans
Immunomodulation
Immunotherapy, Adoptive
Lung Neoplasms
/ etiology
Lymphocytes, Tumor-Infiltrating
/ immunology
Mice, Transgenic
Receptors, Antigen, T-Cell, gamma-delta
/ metabolism
T-Lymphocyte Subsets
/ immunology
T-Lymphocytes, Cytotoxic
/ immunology
Transduction, Genetic
Treatment Outcome
Xenograft Model Antitumor Assays
CTL
FasL
KK-LC-1
T-cell receptor
lung cancer
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Nov 2020
Nov 2020
Historique:
received:
09
07
2020
revised:
07
08
2020
accepted:
09
08
2020
pubmed:
12
8
2020
medline:
22
12
2020
entrez:
12
8
2020
Statut:
ppublish
Résumé
The present study analyzed the antitumor effect of γδT cells transduced with the TCR of cancer-specific CTLs to establish forceful cancer-specific adoptive immunotherapy. We cloned the TCRαβ genes from CTLs showing HLA-B15 restricted recognition of Kita-Kyushu lung cancer antigen-1 (KK-LC-1), a cancer/germline gene antigen, identified in a lung adenocarcinoma case (F1121). The TCRαβ and CD8 genes were transduced into γδT cells induced from PBLs of healthy volunteers stimulated with zoledronate and IL-2. The KK-LC-1-specific TCRαβ-CD8 γδT cells showed cytotoxic activity against the KK-LC-1 positive lung cancer cell line F1121L and produced IFN-γ against F1121L and KK-LC-1 peptide-pulsed F1121 EBV-B cells. These responses were blocked by HLA class I and HLA-B/C antibodies. An in vivo assay using NOD/SCID mice with xenotransplantation of human lung cancer cells was performed, and the TCRαβ-CD8 transduced γδT cells (TCRαβ-CD8 γδT cells) were intravenously injected. Growth inhibition of KK-LC-1
Identifiants
pubmed: 32780528
doi: 10.1111/cas.14612
pmc: PMC7648040
doi:
Substances chimiques
Antigens, Neoplasm
0
CT83 protein, human
0
Cytokines
0
Receptors, Antigen, T-Cell, gamma-delta
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4021-4030Subventions
Organisme : Cancer Translational Research Project; Ministry of Health, Labour and Welfare of Japan
Organisme : Cancer Research Institute, UOEH Research Grant for Promotion of Occupational Health
Organisme : Ministry of Education, Culture, Sports, Science and Technology, Japan
ID : JP20390375
Organisme : Ministry of Education, Culture, Sports, Science and Technology, Japan
ID : JP21659327
Organisme : Ministry of Education, Culture, Sports, Science and Technology, Japan
ID : JP18K08806
Organisme : Ministry of Education, Culture, Sports, Science and Technology, Japan
ID : JP19K09294
Informations de copyright
© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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