TY - JOUR
T1 - Potentiation of Tumor Eradication by Adoptive Immunotherapy with T-cell Receptor Gene-Transduced T-Helper Type 1 Cells
AU - Chamoto, Kenji
AU - Tsuji, Takemasa
AU - Funamoto, Hiromi
AU - Kosaka, Akemi
AU - Matsuzaki, Junko
AU - Sato, Takeshi
AU - Abe, Hiroyuki
AU - Fujio, Keishi
AU - Yamamoto, Kazuhiko
AU - Kitamura, Toshio
AU - Takeshima, Tsuguhide
AU - Togashi, Yuji
AU - Nishimura, Takashi
PY - 2004/1/1
Y1 - 2004/1/1
N2 - Adoptive immunotherapy using antigen-specific T-helper type 1 (Th1) cells has been considered as a potential strategy for tumor immunotherapy. However, its application to tumor immunotherapy has been hampered by difficulties in expanding tumor-specific Th1 cells from tumor-bearing hosts. Here, we have developed an efficient protocol for preparing mouse antigen-specific Th1 cells from nonspecifically activated Th cells after retroviral transfer of T-cell receptor (TCR)-α and TCR-β genes. We demonstrate that Th1 cells transduced with the TCR-β and -β genes from the I-A d-restricted ovalbumin (OVA)323-339-specific T-cell clone DO11.10 produce IFN-γ but not interleukin-4 in response to stimulation with OVA323-339 peptides or A20 B lymphoma (A20-OVA) cells expressing OVA as a model tumor antigen. TCR-transduced Th1 cells also exhibited cytotoxicity against tumor cells in an antigen-specific manner. Moreover, adoptive transfer of TCR-transduced Th1 cells, but not mock-transduced Th1 cells, exhibited potent antitumor activity in vivo and, when combined with cyclophosphamide treatment, completely eradicated established tumor masses. Thus, TCR-transduced Th1 cells are a promising alternative for the development of effective adoptive immunotherapies.
AB - Adoptive immunotherapy using antigen-specific T-helper type 1 (Th1) cells has been considered as a potential strategy for tumor immunotherapy. However, its application to tumor immunotherapy has been hampered by difficulties in expanding tumor-specific Th1 cells from tumor-bearing hosts. Here, we have developed an efficient protocol for preparing mouse antigen-specific Th1 cells from nonspecifically activated Th cells after retroviral transfer of T-cell receptor (TCR)-α and TCR-β genes. We demonstrate that Th1 cells transduced with the TCR-β and -β genes from the I-A d-restricted ovalbumin (OVA)323-339-specific T-cell clone DO11.10 produce IFN-γ but not interleukin-4 in response to stimulation with OVA323-339 peptides or A20 B lymphoma (A20-OVA) cells expressing OVA as a model tumor antigen. TCR-transduced Th1 cells also exhibited cytotoxicity against tumor cells in an antigen-specific manner. Moreover, adoptive transfer of TCR-transduced Th1 cells, but not mock-transduced Th1 cells, exhibited potent antitumor activity in vivo and, when combined with cyclophosphamide treatment, completely eradicated established tumor masses. Thus, TCR-transduced Th1 cells are a promising alternative for the development of effective adoptive immunotherapies.
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U2 - 10.1158/0008-5472.CAN-03-2596
DO - 10.1158/0008-5472.CAN-03-2596
M3 - Article
C2 - 14729649
AN - SCOPUS:9144239842
SN - 0008-5472
VL - 64
SP - 386
EP - 390
JO - Cancer research
JF - Cancer research
IS - 1
ER -