Localized Nano-mediated Interleukin-12 Gene Therapy: Promising Candidate for Cancer Immunotherapeutics

Abstract

Background: Interleukin-12 (IL-12) has a pleiotropic nature that allows it to induce immune responses while reversing tumour-induced immunosuppression. Therefore, this paper discusses the application and potential of IL-12 as an antitumor immunotherapeutic agent, emphasizing its advantages and limitations and the need for and the development of localized IL-12 nano-delivery strategies in cancer immunotherapy. Methods: To assess the potential of localized nano-mediated Interleukin-12 gene therapy for cancer treatment, several databases from the National Centre for Biotechnology Information, WorldCat.org and the National Library of Medicine were searched for peer-reviewed studies. Main findings: From the literature search, it was evident that IL-12 is a promising cancer immunotherapeutic agent. However, the systemic delivery of IL-12 was compromised by severe dose-limiting side-effects, prompting the need for localized gene therapy to express the interleukin within the tumour microenvironment while minimizing systematic exposure. Although viral and non-viral gene therapy have demonstrated some efficacy in preclinical trials, the era of nanomedicine has opened novel avenues to improve therapeutic indices with minimal side effects. IL-12 activity can be further potentiated by combination with other anticancer molecules that display immunostimulatory, autoantigenic and cytotoxic properties. Combination therapy has gained significant interest in the last decade as they increase the therapeutic properties of gene therapy by decreasing the threshold for IL-12 efficacy and preventing systematic toxicity. Conclusion: The findings of this article will provide researchers with the knowledge to create immunotherapeutic nanovectors which work synergistically with their therapeutic payload to enhance the therapeutic effect of the IL-12 gene to eliminate cancer cells.

Degradable Cationic Polycarbamates Designed for Robust IL-12 Gene Therapy against Metastatic Lung Cancer

“…It was documented that the IL-12 protein actively initiates the NK cells to secrete the IFN-γ, a cytotoxic cytokine capable of triggering the apoptosis in cancer cells. 35,36 As such, a previous study revealed that 25 kDa LPEI-mediated IL-12 gene delivery effectively extended the survival time of C57BL/6 mice bearing metastatic LLCs. 14 In line with this, the BHE-MDE-mediated IL-12 gene therapy in the mice plays the same function on eliminating metastatic LLCs in the mice, thereby extending their survival time (Figure 5).…”