Intravenous Clec9A-STING liposomes, or intra-tumoral Clec9A-RIG-I liposomes significantly suppressed B16-F10 melanoma growth and induced neo-epitope and survivin-specific CD4<sup>+</sup> and CD8<sup>+</sup> T-cell responses.<h4>Conclusions</h4>Clec9A-STING liposomes are a scalable, translatable tumor-targeted immunotherapy platform. Here, CD4 is linked to melanoma.