Photothermal Therapy Combined with Neoantigen Cancer Vaccination for Effective Immunotherapy against Large Established Tumors and Distant Metastasis

Photothermal therapy (PTT) and neoantigen cancer vaccine each offer minimally invasive and highly specific cancer therapy; however, they are not effective against large established tumors due to physical and biological barriers that attenuate thermal ablation and abolish antitumor immunity. Here, comparative study is designed and performed using small (≈50 mm3) and large (>100 mm3) tumors to examine how tumor size affects the therapeutic efficiency of PTT and neoantigen cancer vaccine. It is shown that spiky gold nanoparticle (SGNP)‐based PTT and synergistic dual adjuvant‐based neoantigen cancer vaccine can efficiently regress small tumors as a single agent, but not large tumors due to limited internal heating and immunosuppressive tumor microenvironment (TME). It is reported that PTT sensitizes tumors to neoantigen cancer vaccination by destroying and compromising the TME via thermally induced cellular and molecular damage, while neoantigen cancer vaccine reverts local immune suppression induced by PTT and shapes residual TME in favor of antitumor immunity. The combination therapy efficiently eradicates large local tumors and also exerts strong abscopal effect against pre‐established distant tumors with robust systemic antitumor immunity. Thus, PTT combined with neoantigen cancer vaccine is a promising nano‐immunotherapy for personalized therapy of advanced cancer.Photothermal therapy and neoantigen cancer vaccine together synergize and improve local tumor ablation, local, and systemic immune activation, and tumor trafficking of effector immune cells, leading to efficient control of large local tumors as well as distant metastatic tumors. Photothermal therapy combined with neoantigen cancer vaccination offers a promising strategy for personalized therapy of advanced cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/169285/1/adtp202100093.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/169285/2/adtp202100093-sup-001-SuppMat.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/169285/3/adtp202100093_am.pd