IL-2 and Beyond in Cancer Immunotherapy

J Interferon Cytokine Res. 2018 Feb;38(2):45-68. doi: 10.1089/jir.2017.0101.


The development of the T- and natural killer (NK) cell growth factor IL-2 has been a sentinel force ushering in the era of immunotherapy in cancer. With the advent of clinical grade recombinant IL-2 in the mid-1980s, oncologists could for the first time directly manipulate lymphocyte populations with systemic therapy. By itself, recombinant IL-2 can induce clinical responses in up to 15% of patients with metastatic cancer or renal cell carcinoma. When administered with adoptively transferred tumor-reactive lymphocytes, IL-2 promotes T cell engraftment and response rates of up to 50% in metastatic melanoma patients. Importantly, these IL-2-driven responses can yield complete and durable responses in a subset of patients. However, the use of IL-2 is limited by toxicity and concern of the expansion of T regulatory cells. To overcome these limitations and improve response rates, other T cell growth factors, including IL-15 and modified forms of IL-2, are in clinical development. Administering T cell growth factors in combination with other agents, such as immune checkpoint pathway inhibitors, may also improve efficacy. In this study, we review the development of T- and NK cell growth factors and highlight current combinatorial approaches based on these reagents.

Keywords: IL-15; IL-2; T cells; adoptive cellular therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Immunotherapy*
  • Interleukin-2 / immunology*
  • Neoplasms / immunology*
  • Neoplasms / therapy*


  • Interleukin-2