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In vivo functional efficacy of tumor-specific T cells expanded using HLA-Ig based artificial antigen presenting cells (aAPC)

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Abstract

Adoptive immunotherapy for treatment of cancers and infectious diseases is often hampered by a high degree of variability in the final T cell product and in the limited in vivo function and survival of ex vivo expanded antigen-specific cytotoxic T cells (CTL). This has stimulated interest in development of standardized artificial antigen presenting cells (aAPC) to reliably expand antigen specific CTL. However, for successful immunotherapy the aAPC ex vivo generated CTL must have anti-tumor activity in vivo. Here, we demonstrate that HLA-Ig based aAPC stimulated tumor-specific CTL from human peripheral blood T lymphocytes showed robust expansion and functional activity in a human/SCID mouse melanoma model. HLA-Ig based aAPC expanded CTL were detected in the peripheral blood up to 15 days after transfer. Non-invasive bioluminescence imaging of tumor bearing mice demonstrated antigen dependent localization of transferred CTL to the tumor site. Moreover, adoptive transfer of HLA-Ig based aAPC generated CTL inhibited the tumor growth both in prevention and treatment modes of therapy and was comparable to that achieved by dendritic cell expanded CTL. Thus, our data demonstrate potential therapeutic in vivo activity of HLA-Ig based aAPC expanded CTL to control tumor growth.

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Abbreviations

aAPC:

artificial Antigen presenting cell

Mart-1:

Melanoma antigen recognized by T cells-1

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Acknowledgments

We thank Carl H June for providing anti-human CD28 antibody (clone 9.3), Drew Bennett for making HLA-A2 Ig dimer, and Richard Senatore for help with cell culture. This work has been supported by grants from National Institutes of Health, Bethesda, Maryland to JPS (AI 44129, CA108835 and AI 29575).

Conflict of interest statement

The authors declare that they have no commercial and financial interests.

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Authors and Affiliations

  1. Department of Pathology, Johns Hopkins School of Medicine, Ross 664G, 720 Rutland Avenue, Baltimore, MD, 21205, USA

    Malarvizhi Durai, Mathias Oelke & Jonathan P. Schneck

  2. Department of Gastroenterology, Medizinische Hochschule Hannover, Hannover, Germany

    Christine Krueger

  3. Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, USA

    Zhaohui Ye & Linzhao Cheng

  4. Department of Internal Medicine 5, Hematology and Oncology, University of Erlangen-Nuernberg, Erlangen, Germany

    Andreas Mackensen

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  1. Malarvizhi Durai
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  2. Christine Krueger
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  4. Linzhao Cheng
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Correspondence to Malarvizhi Durai or Jonathan P. Schneck.

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Durai, M., Krueger, C., Ye, Z. et al. In vivo functional efficacy of tumor-specific T cells expanded using HLA-Ig based artificial antigen presenting cells (aAPC). Cancer Immunol Immunother 58, 209–220 (2009). https://doi.org/10.1007/s00262-008-0542-1

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