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Promising γ-Chain Cytokines for Cancer Immunotherapy

Interleukins-7, -15, and -21 as Vaccine Adjuvants, Growth Factors, and Immunorestoratives

  • Chapter
Immunotherapy of Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

The molecular identification of a plethora of T-cell tumor antigens that can serve as targets for many human cancers, and the clinical development of techniques to administer tumor vaccines represent important advances toward the development of T-cell-specific immunotherapy for cancer. Despite this progress, current clinical results demonstrate that tumor vaccines, as single agents, are generally not potent enough to induce regression of existing tumors or long lasting enough to provide durable adjuvant benefit. Similarly, the full effectiveness of adoptive cellular therapies for cancer immunotherapy has not yet been realized because of difficulties in sustaining T-cells in vivo following adoptive transfer. Thus, the present challenge for the field of tumor immunology is to develop clinically applicable approaches for amplifying the T-cell-specific immunity induced by tumor vaccines and for augmenting survival of cells delivered in the context of adoptive therapies. The family of cytokines that signals through the common cytokine γ-chain (γc) demonstrates potent effects on T-cell development, expansion, and viability. Interleukin (IL)-2, a prototypic member of this family, has already demonstrated antitumor effects in some settings. However, recent studies have demonstrated that other members of the γc cytokine family possess characteristics that render them more favorable than IL-2 for amplifying T-cell-specific immunity toward tumors. IL-7, IL-15, and IL-21 have all shown promise in preclinical models of tumor immunotherapy. IL-7 is notable for its capacity to serve as an immunorestorative agent, as well as its ability to augment both CD4 and CD8 immune responses, with a particular capacity to amplify lowaffinity, subdominant immune responses that are characteristically induced by tumor antigens. IL-15 provides potent survival and differentiation signals to both CD8 memory cells and natural-killer cells, features that are likely to be translatable in the context of both tumor vaccines and adoptive immunotherapy. IL-21 is less well studied than IL-7 or IL-15, but appears able to amplify responses to other cytokines, especially IL-15, thus further augmenting effector and memory cell expansion. Thus, a large amount of preclinical data suggest that integration of one or several new γc cytokines into immunotherapy regimens for cancer will play an important role in moving this field closer to clinical efficacy.

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  1. Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD

    Terry J. Fry MD & Crystal L. Mackall MD

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  1. University of Washington School of Medicine, Seattle, WA

    Mary L. Disis MD

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Fry, T.J., Mackall, C.L. (2006). Promising γ-Chain Cytokines for Cancer Immunotherapy. In: Disis, M.L. (eds) Immunotherapy of Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1385/1-59745-011-1:397

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