BSA-LDHs-cGAMP In Situ Sensitization of Osteosarcoma: Enhancing Antitumor Efficacy with CD40 Agonist Antibodies

Osteosarcoma is a malignant bone tumor that is extremely aggressive and presents several therapeutic problems. Although CD40 agonist antibodies (αCD40) have demonstrated potential in improving T cell priming and reprogramming tumor-associated macrophages, osteosarcoma's poor immunogenicity leads to "cold" tumors that are challenging to cure. When it comes to triggering immunological responses, the STING pathway is essential. To further improve this impact, cGAMP was stabilized and delivered using layered double hydroxide (LDH) nanoparticles cross-linked with bovine serum albumin (BSA). BSA-LDHs-cGAMP improved the infiltration of CD40+ macrophages and DC cells, which, in turn, improved the therapeutic impact of αCD40 immunotherapy. These results offer a promising in situ cancer treatment and show the possibility of αCD40 boosters in bone tumor therapy.