| RRC ID |
81318
|
| Author |
Fujiki F, Morimoto S, Nishida Y, Tanii S, Aoyama N, Inatome M, Inoue K, Katsuhara A, Nakajima H, Nakata J, Nishida S, Tsuboi A, Oka Y, Oji Y, Sogo S, Sugiyama H.
|
| Title |
Establishment of a novel NFAT-GFP reporter platform useful for the functional avidity maturation of HLA class II-restricted TCRs.
|
| Journal |
Cancer Immunol Immunother
|
| Abstract |
CD4+ T cells that recognize antigenic peptides presented on HLA class II are essential for inducing an optimal anti-tumor immune response, and adoptive transfer of tumor antigen-specific TCR-transduced CD4+ T cells with high responsiveness against tumor is a promising strategy for cancer treatment. Whereas a precise evaluation method of functional avidity, an indicator of T cell responsiveness against tumors, has been established for HLA class I-restricted TCRs, it remains unestablished for HLA class II-restricted TCRs. In this study, we generated a novel platform cell line, CD4-2D3, in which GFP reporter was expressed by NFAT activation via TCR signaling, for correctly evaluating functional avidity of HLA class II-restricted TCRs. Furthermore, using this platform cell line, we succeeded in maturating functional avidity of an HLA class II-restricted TCR specific for a WT1-derived helper peptide by substituting amino acids in complementarity determining region 3 (CDR3) of the TCR. Importantly, we demonstrated that transduction of an avidity-maturated TCR conferred strong cytotoxicity against WT1-expressing leukemia cells on CD4+ T cells, compared to that of its original TCR. Thus, CD4-2D3 cell line should be useful not only to evaluate TCR functional avidity in HLA class II-restricted TCRs but also to screen appropriate TCRs for clinical applications such as cancer immunotherapy.
|
| Volume |
72(7)
|
| Pages |
2347-2356
|
| Published |
2023-7-1
|
| DOI |
10.1007/s00262-023-03420-8
|
| PII |
10.1007/s00262-023-03420-8
|
| PMID |
36939853
|
| PMC |
PMC10264488
|
| MeSH |
Antigens, Neoplasm
CD4-Positive T-Lymphocytes
Humans
Immunotherapy, Adoptive* / methods
Neoplasms*
Receptors, Antigen, T-Cell / genetics
Receptors, Antigen, T-Cell / metabolism
|
| Resource |
| DNA material |
CSII-EF-MCS-IRES2-Venus (RDB04384)
pCMV-VSV-G-RSV-Rev (RDB04393)
pCAG-HIVgp (RDB04394) |
