Treatment of primary and metastatic tumors through cancer immunotherapy and abscopal effect by targeted antigen-capturing nanoparticles with programmed death-1 blockade

Microcapsules that release antigen-capturing nanoparticles (AC-NPs) with macrophage inflammatory protein-3 alpha (MIP-3$\alpha$) and anti-programmed death-1 (PD-1) antibody are developed, and these microcapsules have the ability to enhance immunoresponses through cross-priming of cluster of differentiation 8+ (CD8+) T cells by dendritic cells (DCs) in vivo in BALB/c mice.

Lipid protamine hyaluronic acid nanoparticles containing AC-NPs generated via nanoprecipitation of 4 mg/mL of polylactic-co-glycolic acid (PLGA), 1,000 ng/mL of MIP-3$\alpha$ and 400 $\mu$g of anti-PD-1 were mixed with 1 mL of 4.0% alginate and 3.0% of hyaluronate and then sprayed with 0.5 mM of ferrous chloride. These capsules were injected subcutaneously around LM17 tumor in the left hind legs of BALB/c mice. The tumors were exposed to a radiation dose of 10 or 20 Gy from 100 keV soft X-ray radiation. PLGA AC-NPs and MIP-3$\alpha$ were released in response to the radiation dose.

PLGA AC-NPs captured tumor-derived protein antigens are released by exposure to radiation, and these antigens were transported to DCs that were recruited and activated by MIP-3$\alpha$, intensifying the DC-associated cross-priming of CD8+ T cells. These treatments resulted in increased antitumor effect and reduced metastasis by abscopal effect. Our targeted immunotherapy may lead to better tumor therapy.