Targeted Delivery of IL-۱۲ for Cancer Immunotherapy

Introduction: In recent years, immunotherapy has revolutionizedthe treatment of several types of cancer, and cytokinebasedimmunotherapy has become one of the most effective approachesin cancer treatment. Interleukin-۱۲ (IL-۱۲), as a type۱ cytokine with potent tumor-suppressive activity, plays a significantrole in the development of efficient immune responsesagainst tumors and has been shown to be a promising candidatefor cancer immunotherapy. IL-۱۲ promotes antigen presentationto activate anti-tumor immunity, leading to an increasedproduction of IFN-γ and the clearance of tumors by activatingthe Th۱ response, a requirement for cytotoxic T and NK cellactivation. IL-۱۲, therefore, plays a significant role in the developmentof efficient immune responses against tumors.The main body: So far, several preclinical models have demonstratedrobust anticancer responses following IL-۱۲ systemicadministration. However, due to the IL-۱۲ dose-dependent toxicity,it appeared to be widely intolerable. Therefore, its use regardingthis approach is clinically limited. To improve the deliveryof IL-۱۲ into the tumor microenvironment and decreasesystemic exposure, more effective systems for targeted delivery,increased maintenance inside the tumor, and less toxicityare required.Different targeting methods have demonstrated effective antitumoractivities of IL-۱۲ with fewer side-effects; among them,some have entered the clinical phase. Over the last decade,combination immunotherapy approaches have attracted a lotof attention. Recent researches suggest that employing targeteddelivery techniques for IL-۱۲ in conjunction with other immunotherapymethods, such as CAR-T cells, PD-۱/PD-L۱ checkpointblockades, and cancer vaccines, could improve the efficacyof therapy in preclinical models of different type of cancers.Conclusion: and future directionsIn light of the advancements noted above and still increasingprogress, it is emerging that targeted delivery technologiescould be the key concern in IL-۱۲ renaissance, enabling thisdistinct cytokine to demonstrate its remarkable therapeutic potential.

کلیدواژه ها:

Immunotherapy ، IL-۱۲ ، Targeted delivery ، CAR-Tcell ، Checkpoint blockade ، Vaccines