Biomimetic cytomembrane nanovaccines prevent breast cancer development in the long term

Cytomembrane cancer nanovaccines are considered a promising approach to induce tumor-specific immunity. Most of the currently developed nanovaccines, unfortunately, fail to study the underlying mechanism for cancer prevention and therapy, as well as immune memory establishment, with their long-term anti-tumor immunity remaining unknown. Here, we present a strategy to prepare biomimetic cytomembrane nanovaccines (named CCMP@R837) consisting of antigenic cancer cell membrane (CCM)-capped poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with imiquimod (R@837) as an adjuvant to activate the immune system. We found that our CCMP@R837 system enhanced bone-marrow-derived dendritic cell uptake and maturation, as well as increased anti-tumor response against breast cancer 4T1 cells in vitro. Moreover, an immune memory was established after three-time immunization with CCMP@R837 in BALB/c mice. The CCMP@R837-immunized BALB/c mice exhibited suppressed tumor growth and a long survival period (75% of mice lived longer than 50 days after tumor formation). This long-term anti-tumor immunity was achieved by increasing CD8⁺ T cells and decreasing regulatory T cells in the tumor while increasing effector memory T cells in the spleen. Overall, our platform demonstrates that CCMP@R837 can be a potential candidate for preventive cancer vaccines in the clinic.