An in vivo combined induction strategy of whole cancer cell vaccines triggers systemic immunity to eradicate triple-negative breast cancer

Triple-negative breast cancer (TNBC) represents the most challenging subtypes of breast cancer, facing the clinical challenges of chemotherapeutic toxicity and immune related adverse events. Traditional therapeutic cancer vaccines, which have relatively low toxicity, also fail, due to a lack of vaccine immunogenicity. Herein, we developed an in vivo combined induction strategy of whole cancer cell vaccines (WCVs), based on sialic acid (SA)-L-selectin axis-mediated in vivo live-cell nano-drug delivery system (LCNDDS). Antigen inducers (melittin and mitoxantrone) precisely targeted tumors via the in vivo LCNDDS, and collectively facilitated the whole release of tumor antigens, particularly tumor cell membrane antigens. This process activated dendritic cells and helper T lymphocytes, depleted myeloid-derived suppressor cells, and generated active cytotoxic T lymphocytes and natural killer cells, thereby showing an “optimus prime” tumor inhibition index. Furthermore, the WCVs co-induced in vivo nearly eradicated both early and advanced TNBC, extended the survival of mice, and established robust immune memory to prevent secondary sepsis in advanced cancer, with excellent biological safety. In summary, the in vivo combined induction strategy of WCVs based on SA-L-selectin axis can trigger systemic immune activation to eradicate TNBC. Our findings present a novel strategy for addressing the clinical challenges of TNBC.