An efficient method to prepare T cell receptor gene-transduced cytotoxic T lymphocytes type 1 applicable to tumor gene cell-therapy.
Genes encoding 2C T cell receptor (TCR) alpha, beta chains from H-2(b)-restricted L(d)-specific CD8(+) cells were successfully transduced into polyclonally activated CD8(+) cells by retroviral modification to generate antigen-specific cytotoxic T lymphocytes (CTL). Antigen-nonspecific CD8(+) T cells polyclonally expanded in the presence of interleukin (IL)-2, Th1 cytokines (interferon (IFN)-gamma and IL-12) and anti-IL-4 monoclonal antibody showed neither cytokine production nor cytotoxicity in response to L(d)-expressing P815 tumor cells. However, 2C-TCR gene-modified CD8(+) T cells exhibited both IFN-gamma production and cytotoxicity in response to P815 tumor cells. The antitumor activity of TCR gene-modified Tc1 cells was also demonstrated in vivo by Winn's assay. Thus, we have developed an efficient method to induce TCR gene-modified antigen-specific Tc1 cells that exhibit antitumor activity both in vitro and in vivo.
Tsuji
Takemasa
T
Division of Immunoregulation, Section of Disease Control, Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815, Japan.
Chamoto
Kenji
K
Funamoto
Hiromi
H
Kosaka
Akemi
A
Matsuzaki
Junko
J
Abe
Hiroyuki
H
Fujio
Keishi
K
Yamamoto
Kazuhiko
K
Kitamura
Toshio
T
Togashi
Yuji
Y
Koda
Toshiaki
T
Nishimura
Takashi
T
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D064987:Cell- and Tissue-Based Therapy; D016207:Cytokines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism; D015316:Genetic Therapy; D008223:Lymphoma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D034801:Mastocytoma / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000302:isolation & purification / Q000627:therapeutic use; D012190:Retroviridae / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000637:transplantation
D016207:Cytokines; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064655:V(D)J recombination activating protein 2