Advancements and challenges in immunocytokines:A new arsenal against cancer  

作　　者：Wenqiang Shi Nan Liu Huili Lu 

机构地区：[1]Shanghai Frontiers Science Center of Drug Target Identification and Delivery,National Key Laboratory of Innovative Immunotherapy,School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240,China [2]Engineering Research Center of Cell&Therapeutic Antibody,Ministry of Education,School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240,China [3]Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China

出　　处：《Acta Pharmaceutica Sinica B》2024年第11期4649-4664,共16页药学学报（英文版）

基　　金：Natural Science Foundation of Chongqing(2022NSCQ-MSX2319 to Dr.Huili Lu,China);Science&Technology Commission of Shanghai Municipality(Nos.21S11906300 and 23ZR1431800 to Dr.Huili Lu,China).

摘　　要：Immunocytokines,employing targeted antibodies to concentrate cytokines at tumor sites,have shown potential advantages such as prolonged cytokine half-lives,mitigated adverse effects,and synergistic antitumor efficacy from both antibody and cytokine components.First,we present an in-depth analysis of the advancements of immunocytokines evaluated in preclinical and clinical applications.Notably,anti-PD-1-based immunocytokines can redirect cytokines to intratumoral CD8^(+)T cells and reinvigorate them to elicit robust antitumor immune responses.Then,we focus on their molecular structures and action mechanisms,striving to elucidate the correlations between diverse molecular structures and their antitumor efficacy.Moreover,our exploration extends to the realm of novel cytokines,including IL-10,IL-18,and IL-24,unraveling their potential in the construction of immunocytokines.However,safety concerns remain substantial barriers to immunocytokines'development.To address this challenge,we explore potential strategies,such as cytokine engineering and prodrug design,which can foster next-generation immunocytokines development.Overall,this review concentrates on the design of molecular structures in immunocytokines,underscoring the direction and focus of ongoing efforts to improve safety profiles while maximizing therapeutic efficacy.

关 键 词：Immunocytokines Bifunctional fusion proteins Combination therapy Cytokine engineering Tumor-conditional PRODRUG 

分 类 号：R73[医药卫生—肿瘤]