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Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Review Article

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

Author(s): Jeaneen Venkatas and Moganavelli Singh*

Volume 22, Issue 10, 2022

Published on: 27 July, 2022

Page: [825 - 842] Pages: 18

DOI: 10.2174/1568009622666220609115109

Price: $65

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: Several databases from the National Centre for Biotechnology Information, WorldCat.org and the National Library of Medicine were searched for peer-reviewed studies to assess the potential of localized nano-mediated interleukin-12 gene therapy for cancer treatment.

Results: The literature search showed 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 with other anticancer molecules that display immunostimulatory, autoantigenic and cytotoxic properties. Combination therapy has gained significant interest in the last decade as it increases gene therapy's therapeutic properties 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.

Keywords: Cancer, gene therapy, immunotherapy, interleukin-12, nano-delivery, nanomedicine.

Graphical Abstract
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