CD137-guided isolation and expansion of antigen-specific CD8 cells for potential use in adoptive immunotherapy

Kazue Watanabe, Susumu Suzuki, Michi Kamei, Shingo Toji, Takakazu Kawase, Toshitada Takahashi, Kiyotaka Kuzushima, Yoshiki Akatsuka

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The efficient isolation and ex vivo expansion of antigen-specific T cells are crucial for successful adoptive immunotherapy against uncontrollable infections and cancers. Several methods have been reported for this purpose, for example, employing MHC-multimeric complexes, interferon-gamma secretion, and antibodies specific for molecules expressed on T-cell surfaces, including CD25, CD69, CD107a, CD137, and CD154. Of the latter, CD137 has been shown to be one of the most promising targets since it is only expressed on CD8+ T cells early after encountering antigen, while being almost undetectable on resting cells. However, detailed comparisons between CD137-based and other methods have not yet been conducted. In this study, we therefore compared three approaches (with CD137, CD107a, and tetramers) using HLA-A24-restricted CMV pp65 and EBV BRLF1 epitopes as model antigens. We found that the CD137-based isolation of antigen-stimulated CD8+ T cells was comparable to tetramer-based sorting in terms of purity and superior to the other two methods in terms of subsequent cell expansion. The method was less applicable to CD4+ T cells since their CD137 upregulation is not sufficiently high. Collectively, this approach is most likely to be optimal among the methods tested for the isolation and expansion of antigen-specific CD8+ cells.

Original languageEnglish
Pages (from-to)311-320
Number of pages10
JournalInternational Journal of Hematology
Volume88
Issue number3
DOIs
Publication statusPublished - 01-10-2008

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CD8 Antigens
Adoptive Immunotherapy
T-Lymphocytes
Antigens
HLA-A24 Antigen
Human Herpesvirus 4
Interferon-gamma
Epitopes
Up-Regulation
Antibodies
Infection
Neoplasms

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Watanabe, Kazue ; Suzuki, Susumu ; Kamei, Michi ; Toji, Shingo ; Kawase, Takakazu ; Takahashi, Toshitada ; Kuzushima, Kiyotaka ; Akatsuka, Yoshiki. / CD137-guided isolation and expansion of antigen-specific CD8 cells for potential use in adoptive immunotherapy. In: International Journal of Hematology. 2008 ; Vol. 88, No. 3. pp. 311-320.
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Watanabe, K, Suzuki, S, Kamei, M, Toji, S, Kawase, T, Takahashi, T, Kuzushima, K & Akatsuka, Y 2008, 'CD137-guided isolation and expansion of antigen-specific CD8 cells for potential use in adoptive immunotherapy', International Journal of Hematology, vol. 88, no. 3, pp. 311-320. https://doi.org/10.1007/s12185-008-0134-z

CD137-guided isolation and expansion of antigen-specific CD8 cells for potential use in adoptive immunotherapy. / Watanabe, Kazue; Suzuki, Susumu; Kamei, Michi; Toji, Shingo; Kawase, Takakazu; Takahashi, Toshitada; Kuzushima, Kiyotaka; Akatsuka, Yoshiki.

In: International Journal of Hematology, Vol. 88, No. 3, 01.10.2008, p. 311-320.

Research output: Contribution to journalArticle

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AU - Suzuki, Susumu

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AU - Takahashi, Toshitada

AU - Kuzushima, Kiyotaka

AU - Akatsuka, Yoshiki

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