Engineering immune cells with membrane-fusogenic liposomes: A new frontier in adoptive cell therapy

Abstract

Adoptive cell therapy continues to encounter diverse hurdles in treating solid tumors, including poor infiltration, an immunosuppressive microenvironment, and tumor immune evasion, necessitating the endowment of effector cells with multiple functionalities. However, conventional cell-engineering techniques, including genetic editing and chemical modification, usually modulate a single functional axis to yield a monofunctional effector cell that can overcome only one physiological barrier, leading to insufficient solid tumor suppression. Recently, membrane-fusogenic liposomes have emerged as a multiplex engineering tool capable of directly producing multifunctional effector cells to simultaneously surmount multiple challenges for effective antitumor efficacy. Through a fusion process, this liposome concurrently achieves immune cell surface functionalization and intracellular delivery of bioactive molecules, thereby endowing effector cells with multiple functionalities within a single step. This minireview summarizes recent advances in the use of fusogenic liposomes for immune cell engineering to boost their therapeutic efficacy against solid tumors. We discuss their design principles and representative applications, and analyze their technical advantages and current limitations. Looking forward, we propose that membrane-fusogenic liposomes hold potential to advance the development of multimodal engineered immune cells for next-generation cancer immunotherapies.