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Functional inactivation of CD4+CD25high regulatory T cells using low dose human/mouse chimeric anti-CD25 monoclonal antibody enhanced lymphokine-activated killer cells activity

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Abstract

Functional modulation of regulatory T cells (T-regs) is one possible approach to cancer immunotherapy. In this study, we investigated whether low-dose basiliximab, a chimeric anti-CD25 monoclonal antibody, could suppress the T-regs function not by depletion but by inactivation, and increase immune responses. Peripheral blood mononuclear cells from healthy donors and patients with malignancy were collected. We tried T-regs inactivation using various concentrations of basiliximab before induction of lymphokine-activated killer (LAK) cells. We measured cell proliferation, lymphocyte phenotype, intracellular T-regs maker, and Th1/2 cytokines production. Our results showed that the optimal concentration of basiliximab for specifically down-modulating only T-regs was 0.001 μg/ ml. The reduction of Th-2 cytokine secretion with concomitant APC induction without suppressing cell proliferation offers the promise of a novel adoptive immunotherapy to cancer patients.

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Acknowledgements

We thank Ms. Y. Nakatani, M. Funada, and M. Okamura for excellent technical assistance. This study proceeded at the Analysis Center for Life Science, Hiroshima University.

Conflict of interest statement

No funds were received in support of this study.

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Authors and Affiliations

  1. Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima, 734-8553, Japan

    Riki Okita, Yoshiyuki Yamaguchi, Masahiro Ohara, Takuhiro Ikeda, Ichiro Nagamine, Akiko Emi, Yoshiharu Kawabuchi, Jun Hihara & Morihito Okada

  2. Department of Breast Oncology, Saitama Medical University, Yamane 1397-1, Hidaka, Saitama, 350-1298, Japan

    Kazuo Matsuura

Authors
  1. Riki Okita
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  2. Yoshiyuki Yamaguchi
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  3. Masahiro Ohara
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  4. Takuhiro Ikeda
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  5. Ichiro Nagamine
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  9. Morihito Okada
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  10. Kazuo Matsuura
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Correspondence to Riki Okita.

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Okita, R., Yamaguchi, Y., Ohara, M. et al. Functional inactivation of CD4+CD25high regulatory T cells using low dose human/mouse chimeric anti-CD25 monoclonal antibody enhanced lymphokine-activated killer cells activity. Targ Oncol 3, 227–234 (2008). https://doi.org/10.1007/s11523-008-0095-4

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  • DOI: https://doi.org/10.1007/s11523-008-0095-4

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