IL-12 enhances efficacy and shortens enrichment time in cytokine-induced killer cell immunotherapy.
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.
Helms
Mike W
MW
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305-5439, USA.
Prescher
Jennifer A
JA
Cao
Yu-An
YA
Schaffert
Steven
S
Contag
Christopher H
CH
D000818:Animals; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D004359:Drug Therapy, Combination; D016219:Immunotherapy, Adoptive; D018664:Interleukin-12 / Q000008:administration & dosage* / Q000009:adverse effects; D007694:Killer Cells, Natural / Q000276:immunology; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D051379:Mice; D008815:Mice, Inbred Strains; D012074:Remission Induction; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D018664:Interleukin-12