A Bioinspired Approach to Next-Generation Vaccines in Solid Tumors with Engineered Cell Membranes.

In solid tumors, the immunosuppressive tumor microenvironment and antigenic heterogeneity pose important challenges for effective immunotherapy, often leading to limited T-cell infiltration and inadequate immune activation. To overcome these barriers in solid tumors, the development of next-generation vaccines capable of eliciting robust and durable anti-tumor immunity has constituted a major focus in the clinic. A promising strategy involves a bioinspired approach that functionalizes synthetic nanocarriers with native cell membranes. These engineered platforms are designed to preserve the surface properties of native cell membranes (immune cells, nonimmune cells, and hybrid cell membranes) to enhance antigen presentation, prolong systemic circulation, and improve biocompatibility. This study systematically examines the design principles and mechanisms of bioinspired vaccines with native cell membranes, highlighting their capability to integrate multiple antigenic and adjuvant signals for superior antigen presentation and T-cell activation. We further explore the synergistic therapeutic effects of the next-generation vaccines when combined with common anti-tumor therapies. Moreover, the primary challenges for their clinical translation in solid tumors are critically discussed. These bioinspired nanoplatforms represent a transformative direction for developing more effective and personalized immunotherapies for solid tumors.