Generation and Targeting of Human Tumor-Specific Tc1 and Th1 Cells Transduced with a Lentivirus Containing a Chimeric Immunoglobulin T-Cell Receptor

Hiroshi Gyobu, Takemasa Tsuji, Yoshinori Suzuki, Takayuki Ohkuri, Kenji Chamoto, Masahide Kuroki, Hiroyuki Miyoshi, You Kawarada, Hiroyuki Katoh, Tsuguhide Takeshima, Takashi Nishimura

Research output: Contribution to journalArticle

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Abstract

CD4+ Th cells, in particular IFN-γ-producing Th1 cells, play a critical role in the activation and maintenance of Tc1 cells that are essential for tumor eradication. Here, we report the generation of artificial tumor-specific Th1 and Tc1 cells from nonspecifically activated T cells using a lentiviral transduction system. Anti-CD3-activated T cells from healthy human donors were transduced with a lentivirus containing a chimeric immunoglobulin T-cell receptor gene composed of single-chain variable fragments derived from an anticarcinoembryonic antigen (CEA)-specific monoclonal antibody fused to an intracellular signaling domain derived from the cytoplasmic portions of membrane-bound CD28 and CD3ζ. These artificial tumor-specific Tc1 and Th1 cells, termed Tc1- and Th1-T bodies, respectively, could be targeted to CEA + tumor cells independently of MHC restriction. Specifically, Tc1-T bodies demonstrated high cytotoxicity and produced IFN-γ in response to CEA+ tumor cell lines but not CEA+ tumors. Although Th1-T bodies exhibited low cytotoxicity, they secreted high levels of IFN-γ and interleukin-2 in response to CEA+ tumor cells. Such CEA+ tumor-specific activation was not observed in mock gene-transduced nonspecific Tc1 and Th1 cells. Moreover, Tc1- and Th1-T bodies exhibited strong antitumor activities against CEA+ human lung cancer cells implanted into RAG2-/- mice. Furthermore, combined therapy with Tc1- and Th1-T bodies resulted in enhanced antitumor activities in vivo. Taken together, our findings demonstrate that Tc1- and Th1-T bodies represent a promising alternative to current methods for the development of effective adoptive immunotherapies.

Original languageEnglish (US)
Pages (from-to)1490-1495
Number of pages6
JournalCancer Research
Volume64
Issue number4
DOIs
StatePublished - Feb 15 2004

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Lentivirus
Th1 Cells
T-Cell Antigen Receptor
Immunoglobulins
Neoplasms
T-Lymphocytes
Adoptive Immunotherapy
T-Cell Receptor Genes
Single-Chain Antibodies
Immunoglobulin Genes
Tumor Cell Line
Interleukin-2
Lung Neoplasms
Monoclonal Antibodies
Maintenance
Cell Membrane
Antigens
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Generation and Targeting of Human Tumor-Specific Tc1 and Th1 Cells Transduced with a Lentivirus Containing a Chimeric Immunoglobulin T-Cell Receptor. / Gyobu, Hiroshi; Tsuji, Takemasa; Suzuki, Yoshinori; Ohkuri, Takayuki; Chamoto, Kenji; Kuroki, Masahide; Miyoshi, Hiroyuki; Kawarada, You; Katoh, Hiroyuki; Takeshima, Tsuguhide; Nishimura, Takashi.

In: Cancer Research, Vol. 64, No. 4, 15.02.2004, p. 1490-1495.

Research output: Contribution to journalArticle

Gyobu, H, Tsuji, T, Suzuki, Y, Ohkuri, T, Chamoto, K, Kuroki, M, Miyoshi, H, Kawarada, Y, Katoh, H, Takeshima, T & Nishimura, T 2004, 'Generation and Targeting of Human Tumor-Specific Tc1 and Th1 Cells Transduced with a Lentivirus Containing a Chimeric Immunoglobulin T-Cell Receptor', Cancer Research, vol. 64, no. 4, pp. 1490-1495. https://doi.org/10.1158/0008-5472.CAN-03-2780
Gyobu, Hiroshi ; Tsuji, Takemasa ; Suzuki, Yoshinori ; Ohkuri, Takayuki ; Chamoto, Kenji ; Kuroki, Masahide ; Miyoshi, Hiroyuki ; Kawarada, You ; Katoh, Hiroyuki ; Takeshima, Tsuguhide ; Nishimura, Takashi. / Generation and Targeting of Human Tumor-Specific Tc1 and Th1 Cells Transduced with a Lentivirus Containing a Chimeric Immunoglobulin T-Cell Receptor. In: Cancer Research. 2004 ; Vol. 64, No. 4. pp. 1490-1495.
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AU - Suzuki, Yoshinori

AU - Ohkuri, Takayuki

AU - Chamoto, Kenji

AU - Kuroki, Masahide

AU - Miyoshi, Hiroyuki

AU - Kawarada, You

AU - Katoh, Hiroyuki

AU - Takeshima, Tsuguhide

AU - Nishimura, Takashi

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