Download or read book Targeted Combination Therapy of Triple-negative Breast Cancer written by Ketki Bhise and published by . This book was released on 2021 with total page 148 pages. Available in PDF, EPUB and Kindle. Book excerpt: We tested the efficacies of three immune checkpoint inhibitors, namely blockades for CD73, CTLA4 and PD-L1 in combination with LipoDoxAtz to assess reduction in tumor growth. Owing to the possibility that antiPD-L1 and antiCTLA4 act at different stages of the cancer immunity cycle, with CTLA4 blockade at the earlier stage than PD-L1 blockage, the tumors treated with LipoDoxAtz and CTLA4 combination showed a significant reduction in growth compared to the combination with PD-L1. CD73 blockade had no effect in arresting tumor growth. Our data with combination of LipoDoxAtz + CTLA4 showed a significant tumor regression, increased survival and no toxicity to the overall health of mice. Moreover, mechanistic studies indicated upregulation of proteins promoting immunogenic cell death, namely HMGB1 and calreticulin with the combination group. Higher infiltration of CD8+ Tc cells and secretion of IFN-g confirmed the involvement of immunogenic factors to arrest tumor growth in highly aggressive 4T1 tumors. These findings indicate promising therapeutic potentials for our newly developed hypoxia-targeted DoxAtz in combination with antiCTLA4 for effective TNBC therapy in clinic.