Melittin-lipid nanoparticles target to lymph nodes and elicit a systemic anti-tumor immune response

Targeted delivery of a nanovaccine loaded with a tumor antigen and adjuvant to the lymph nodes (LNs) is an attractive approach for improving cancer immunotherapy outcomes. However, the application of this technique is restricted by the paucity of suitable tumor-associated antigens (TAAs) and the sophisticated technology required to identify tumor neoantigens. Here, we demonstrate that a self-assembling melittin-lipid nanoparticle (alpha-melittin-NP) that is not loaded with extra tumor antigens promotes whole tumor antigen release in situ and results in the activation of antigen-presenting cells (APCs) in LNs. Compared with free melittin, alpha-melittin-NPs markedly enhance LN accumulation and activation of APCs, leading to a 3.6-fold increase in antigen-specific CD8(+) T cell responses. Furthermore, in a bilateral flank B16F10 tumor model, primary and distant tumor growth are significantly inhibited by alpha-melittin-NPs, with an inhibition rate of 95% and 92%, respectively. Thus, alpha-melittin-NPs induce a systemic anti-tumor response serving as an effective LN-targeted whole-cell nanovaccine. The bee venom melittin has anti-tumor properties but is unsuitable for therapeutic use on its own. Here, the authors generate melittin-nanoparticles and demonstrate that the nanoparticles reduce tumor growth and generate an anti-tumor immune response.