Pre-treatment with cyclophosphamide or OX40 (CD134) costimulation targeting regulatory T cell function enhances the anti-tumor immune effect of adoptively transferred CD8+ T cells from wild-type mice

  • Authors:
    • Tomoyuki Ueki
    • Satoshi Murata
    • Naomi Kitamura
    • Eiji Mekata
    • Tohru Tani
  • View Affiliations

  • Published online on: July 1, 2009     https://doi.org/10.3892/mmr_00000146
  • Pages: 615-620
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Abstract

Regulatory T cells (Tregs) are a major obstacle to the establishment of effective cancer immunotherapy. As mediators of immune tolerance, they are a critical target for pre-conditioning for adoptive immunotherapy. Here, we show that pre-treatment with cyclophosphamide or agonistic anti-OX40 mAb augments the anti-tumor immune effect of adoptive CD8+ T cell therapy in a clinically relevant wild-type model, as opposed to a TCR-transgenic mouse model. Tumor antigen-stimulated CD8+ T cells (7x106), including a small number (2.17x105) of tumor antigen-specific effector CD8+ T cells, were transferred into tumor-bearing mice. A response was detected in the adoptively transferred antigen-specific CD8+ T cells, but was insufficient for the eradication of the established tumor. However, pre-treatment with cyclophosphamide to reduce Tregs was shown to enhance the anti-tumor immune effect of the adoptively transferred CD8+ T cells. Moreover, we demonstrated for the first time that pre-treatment with OX40 costimulation, with the aim of nullifying Treg-mediated suppression, maintained the tumor-specific immune response of adoptively transferred CD8+ T cells, resulting in the eradication of the established tumor. These findings suggest that pre-conditioning with the aim of depleting Tregs is a useful strategy for adoptive cancer immunotherapy.

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July-August 2009
Volume 2 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Ueki T, Murata S, Kitamura N, Mekata E and Tani T: Pre-treatment with cyclophosphamide or OX40 (CD134) costimulation targeting regulatory T cell function enhances the anti-tumor immune effect of adoptively transferred CD8+ T cells from wild-type mice . Mol Med Rep 2: 615-620, 2009.
APA
Ueki, T., Murata, S., Kitamura, N., Mekata, E., & Tani, T. (2009). Pre-treatment with cyclophosphamide or OX40 (CD134) costimulation targeting regulatory T cell function enhances the anti-tumor immune effect of adoptively transferred CD8+ T cells from wild-type mice . Molecular Medicine Reports, 2, 615-620. https://doi.org/10.3892/mmr_00000146
MLA
Ueki, T., Murata, S., Kitamura, N., Mekata, E., Tani, T."Pre-treatment with cyclophosphamide or OX40 (CD134) costimulation targeting regulatory T cell function enhances the anti-tumor immune effect of adoptively transferred CD8+ T cells from wild-type mice ". Molecular Medicine Reports 2.4 (2009): 615-620.
Chicago
Ueki, T., Murata, S., Kitamura, N., Mekata, E., Tani, T."Pre-treatment with cyclophosphamide or OX40 (CD134) costimulation targeting regulatory T cell function enhances the anti-tumor immune effect of adoptively transferred CD8+ T cells from wild-type mice ". Molecular Medicine Reports 2, no. 4 (2009): 615-620. https://doi.org/10.3892/mmr_00000146