A Review of Clinical and Preclinical Studies on Therapeutic Strategies Using Interleukin-12 in Cancer Therapy and the Protective Role of Interleukin-12 in Hematological Recovery in Chemoradiotherapy

Abstract

Interleukin-12 (IL-12), a heterodimeric glycoprotein with α and β subunits covalently bonded with a disulfide bond, is a potent anticancer agent. Its action is accomplished through a linkage of the adaptive and innate immune responses. IL-12 can promote the recovery of the hematopoietic system after cancer chemoradiotherapy by stimulating the physiological processes of stem cells, including cell proliferation and differentiation, reconstitution of hematopoietic function, and peripheral blood count recovery. We review therapeutic strategies using IL-12 in clinical studies, including single-agent and combination strategies in hematological tumors and solid tumors, and studies on the protective effects of IL-12 in chemoradiotherapy. This review highlights promising therapeutic strategies based on the anticancer role of IL-12 and the potential protective effects of IL-12 for cancer patients receiving chemoradiotherapy.

The repeated administration of rhIL‐12 for 14 weeks in rhesus monkeys: A toxicity assessment

“…A study revealed (Mehrotra et al, 1993) The clinical application of IL-12 is limited due to its adverse reactions. Some researchers attribute IL-12's systemic toxicity mainly to the induction of IFN-γ (Ding et al, 2021).…”

“…IL12 has been extensively applied in the fields of tumor immunotherapy and the prevention or treatment of acute radiation syndrome (Li et al, 2020). However, to conduct further clinical research, it is necessary to follow the relevant guidance principles for nonclinical safety evaluation studies issued by regulatory agencies such as the International Council for Harmonization (ICH), Food and Drug Administration (FDA), or National Medical Products Administration (NMPA) and carry out the work in Good Laboratory Practice (GLP)‐certified laboratories.…”

“…Studies have shown that the toxicity of IL-12 is partly due to its ability to stimulate the production of other cytokines such as interferon-gamma and tumor necrosis factor-alpha, which can cause inflammation and tissue damage. In addition, IL-12 has been found to activate immune cells known as regulatory T cells, which can suppress immune responses and contribute to cytokine toxicity(Mehrotra et al, 1993).…”