Reprogramming Chemoimmunotherapy via Biomimetic Cell Membrane- Clay Platform to Amplify Prime–Boost Antitumor Immunity

Chemoimmunotherapy has emerged as a promising strategy by combining chemotherapy with immunotherapy in cancer treatment. However, conventional chemoimmunotherapy strategies typically administer chemotherapy or immunogenic cell death (ICD)-induced chemotherapy prior to immunotherapy, which can compromise immune responsiveness due to toxicity, drug-induced immunosuppression and insufficient immune memory formation. As a result, therapeutic efficacy is critically influenced by the temporal order of immune activation and cytotoxic treatment. In this work, we reprogram the conventional chemoimmunotherapy sequence by developing an immune-priming-enabled chemoimmunotherapy strategy (immunotherapy prior to trimodal photochemotherapy) using cancer cell membrane-coated layered double hydroxide biomaterials (CCM-LDHs). BSA coated CpG-associated LDHs has been established as an immunomodulatory adjuvant to promote immune responses of CCM and reduce immune escape. By precisely modulating the CCM to LDHs ratio, the biomimetic CCM-LDHs can act as either antigen reservoirs to promote dendritic cell activation and T-cell priming or serve as a homologous tumor targeting to enhance the cellular uptake of drugs to promote their efficacy. In vitro and in vivo studies demonstrate immune priming followed by ICD-induced photochemotherapy provokes stronger cytotoxic T-cell responses and establishes robust immunological memory compared with the conventional ICD-induced chemoimmunotherapy, thereby supporting long-term anti-tumor immune surveillance.