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. 2005 Jul 15;106(2):470-6.
doi: 10.1182/blood-2004-09-3663. Epub 2005 Mar 24.

Generation of tumor-specific, HLA class I-restricted human Th1 and Tc1 cells by cell engineering with tumor peptide-specific T-cell receptor genes

Takemasa Tsuji  1 , Masaki Yasukawa, Junko Matsuzaki, Takayuki Ohkuri, Kenji Chamoto, Daiko Wakita, Taichi Azuma, Hironari Niiya, Hiroyuki Miyoshi, Kiyotaka Kuzushima, Yoshihiro Oka, Haruo Sugiyama, Hiroaki Ikeda, Takashi Nishimura
Affiliations
Free article

Generation of tumor-specific, HLA class I-restricted human Th1 and Tc1 cells by cell engineering with tumor peptide-specific T-cell receptor genes

Takemasa Tsuji et al. Blood. .
Free article

Abstract

Tumor antigen-specific CD4+ and CD8+ T lymphocytes, especially interferon-gamma (IFN-gamma)-producing type-1 helper T (Th1) and type-1 cytotoxic T (Tc1) cells, play a crucial role in tumor eradication. Adoptive transfer using tumor-specific Th1 and Tc1 cells is a promising therapeutic strategy for tumor immunotherapy. However, its clinical application has been hampered because of difficulties in generating tumor-specific Th1 cells from patients with tumors. To overcome this problem, we have developed an efficient method to prepare tumor-specific Th1 and Tc1 cells. T-cell receptor (TCR) alpha and beta genes obtained from an HLA-A24-restricted, Wilms tumor 1 (WT1) peptide-specific Tc clone were lentivirally transduced to polyclonally activated Th1 and Tc1 cells. As expected, TCR gene-modified Tc1 cells showed cytotoxicity and IFN-gamma production in response to peptide-loaded lymphoblastoid cell lines, WT1 gene-transduced cells, and freshly isolated leukemia cells expressing both WT1 and HLA-A24. Surprisingly, we further demonstrated that Th1 cells transduced with HLA-class I-restricted TCR genes also showed both cytotoxicity and cytokine production in an HLA-A24-restricted manner. In contrast to gene-modified Tc1 cells, Th1 cells produced high amounts of interleukin-2 (IL-2) in addition to IFN-gamma, which is beneficial for induction of antitumor cellular immunity. Thus, TCR gene-modified HLA-class I-restricted Th1 and Tc1 cells are a powerful strategy for the application to adoptive immunotherapy of human cancer.

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