IL-12 enhances efficacy and shortens enrichment time in cytokine-induced killer cell immunotherapy |
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Authors: | Mike W Helms Jennifer A Prescher Yu-An Cao Steven Schaffert Christopher H Contag |
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Institution: | (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; |
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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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