Multiantigenic Nanoformulations Activate Anticancer Immunity Depending on Size

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.