NanoAlum based delivery system to formulate <i>in-situ</i> vaccine for personalized breast cancer immunotherapy

In situ vaccines have shown promise in cancer treatment but encounter obstacles such as limited tumor antigen release, immune-suppressive microenvironments, and insufficient antigen processing. To boost the effectiveness of in situ cancer vaccine, the rationally designed delivery technologies are urgently needed for improved immunotherapy. In the current study, NanoAlum based delivery system has been developed which could function for all the courses during the in situ vaccine formation, including immunogenic cancer death (ICD) induction, immunomodulator (R848) loading as well as carriers for autologous antigens. After intratumoral administration, the NanoAlum based delivery system would induce ICD upon near-infrared (NIR) heating for tumor-derived antigens release. The antigens would then be captured by NanoAlum therefore in situ cancer nanovaccine could be formed with the three moieties: autologous antigens by ICD, R848 as immunoadjuvant, and NanoAlum as delivery system. Under this paradigm, the NanoAlum based delivery system would optimize the efficacy of cancer vaccines by enhancing antigenicity, adjuvanticity, and modulation of immune suppression within the tumor microenvironment, thereby initiating a multistep cascade of antitumor responses. <em>In vivo</em> experiments demonstrated that NanoAlum based delivery system would generate complete eradication of primary tumors, potent abscopal effects on distant tumors and long-term immune response against cancer recurrence. More importantly, the safety of all the compositions within the vaccine has been proved by clinical trials, which makes it highly attractive for clinical translation. Overall, the attempt demonstrates the great potential of in situ cancer vaccine based on NanoAlum delivery system in boosting immunotherapy for cancer treatment.