Multiantigenic Nanoformulations Activate Anticancer Immunity Depending on Size

Abstract Nanoparticle‐adjuvanted cancer vaccines are attracting increasing attention because they can induce an effective anticancer immune response. Single‐antigen vaccines are inefficient to inhibit cancer progression due to the heterogeneity of tumors and the antigenicity alteration of tumor‐associated antigens. Therefore, the efficient delivery of multiple antigens to antigen‐presenting cells is an excellent opportunity for strong anticancer immunity. In this study, three immunoadjuvant‐loaded multiantigenic nanoparticles MANPs/R837 with different diameters, i.e., 83, 103, and 122 nm, are prepared through coating of the cancer cell membrane as a source of multiple antigens onto the imiquimod R837‐loaded poly(lactic‐co‐glycolic acid) nanoparticles. The MANP/R837 with a diameter of 83 nm (MANP83/R837) shows the most efficient delivery of the payload to the draining lymph nodes and achieves the best antigen presentation to T lymphocytes. Compared with the other two nanovaccines, MANP83/R837 has a stronger inhibitory effect on tumor growth and metastasis. In the combination therapy with checkpoint blockade therapy using programmed cell death‐1 antibody, MANPs/R837 show effective inhibition against tumor progression, and MANP83/R837 achieves the most exciting effect. Therefore, MANPs/R837, as a promising therapeutic cancer vaccine, demonstrates great prospects in cancer immunotherapy.