Biyomarker yüklü ASC mikroparçacık aşısına konakçının bağışıklık reaksiyonunun incelenmesi

Prophylactic cancer vaccines effectively prevent specific cancers, but therapeutic vaccines have struggled, often requiring adjuvants and carriers. We developed an innovative antigen delivery platform using extracellular ASC-Speck microparticles that leverage inflammasome activation to enhance immune responses against melanoma. Chimeric ASC microparticles with target antigens were created and purified from transfected HEK293 cells, and tested in a melanoma mouse model for further assessment. These microparticles induced inflammatory responses in immune cells similar to traditional adjuvants. Immunizing mice with tumor-associated antigens (TAAs) such as MAGE-A3, Mage-A1, and Mlana, we evaluated cancer vaccine efficacy. Mice inoculated with B16-MAGE-A3 cells showed tumor growth reduction, with protection rates of 40% for MAGE-A3, 50% for Mage-A1, 0% for Mlana (monovalent), and 66% for the trivalent vaccine. Control mice developed tumors despite high anti-MAGE-A3 antibody titers with Freund's adjuvanted antigen. Treated mice showed more CD80+ and fewer CD206+ macrophages, alongside reduced FoxP3+ CD4 T cells, in tumor tissue, indicating anti-tumor immune responses. The ASC-Speck microparticle platform appears to polarize macrophages towards an M1-like phenotype and reduce Tregs, promoting anti-tumor immunity in the tumor microenvironment. Further research is needed to confirm these findings and elucidate underlying mechanisms, highlighting this platform's potential for novel cancer immunotherapies.