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 ...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.展开更多
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).
文摘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.
