Potentiation of tumor eradication by adoptive immunotherapy with T-cell receptor gene-transduced T-helper type 1 cells.
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)-alpha and TCR-beta genes. We demonstrate that Th1 cells transduced with the TCR-alpha and -beta genes from the I-A(d)-restricted ovalbumin (OVA)(323-339)-specific T-cell clone DO11.10 produce IFN-gamma but not interleukin-4 in response to stimulation with OVA(323-339) 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.
Chamoto
Kenji
K
Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan. tak24@imm.hokudai.ac.jp
Tsuji
Takemasa
T
Funamoto
Hiromi
H
Kosaka
Akemi
A
Matsuzaki
Junko
J
Sato
Takeshi
T
Abe
Hiroyuki
H
Fujio
Keishi
K
Yamamoto
Kazuhiko
K
Kitamura
Toshio
T
Takeshima
Tsuguhide
T
Togashi
Yuji
Y
Nishimura
Takashi
T
D000818:Animals; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D016393:Lymphoma, B-Cell / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin