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IL-12 enhances efficacy and shortens enrichment time in cytokine-induced killer cell immunotherapy

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Abstract

Cytokine-induced killer (CIK) cells are T cell derived ex vivo expanded cells with both NK and T cell properties. They exhibit potent anti-tumor efficacy against various malignancies in preclinical models and have proven safe and effective in clinical studies. We combined CIK cell adoptive immunotherapy with IL-12 cytokine immunotherapy in an immunocompetent preclinical breast cancer model. Combining CIK cells with IL-12 increased anti-tumor efficacy in vivo compared to either therapy alone. Combination led to full tumor remission and long-term protection in 75% of animals. IL-12 treatment sharply increased the anti-tumor efficacy of short-term cultured CIK cells that exhibited no therapeutic effect alone. Bioluminescence imaging based in vitro cytotoxicity and in vivo homing assays revealed that short-term cultured CIK cells exhibit full cytotoxicity in vitro, but display different tumor homing properties than fully expanded CIK cells in vivo. Our data suggest that short-term cultured CIK cells can be “educated” in vivo, producing fully expanded CIK cells upon IL-12 administration with anti-tumor efficacy in a mouse model. Our findings demonstrate the potential to improve current CIK cell-based immunotherapy by increasing efficacy and shortening ex vivo expansion time. This holds promise for a highly efficacious cancer therapy utilizing synergistic effects of cytokine and cellular immunotherapy.

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Authors and Affiliations

  1. Molecular Imaging Program, Departments of Pediatrics, Radiology, and Microbiology and Immunology, Stanford University School of Medicine, Clark Center, East Wing E150, 318 Campus Drive, Stanford, CA, 94305-5439, USA

    Mike W. Helms, Jennifer A. Prescher, Yu-An Cao, Steven Schaffert & Christopher H. Contag

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  1. Mike W. Helms
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  2. Jennifer A. Prescher
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Correspondence to Christopher H. Contag.

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Helms, M.W., Prescher, J.A., Cao, YA. et al. IL-12 enhances efficacy and shortens enrichment time in cytokine-induced killer cell immunotherapy. Cancer Immunol Immunother 59, 1325–1334 (2010). https://doi.org/10.1007/s00262-010-0860-y

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