© 2015 Mary Ann Liebert, Inc. Combination immunotherapy has resulted in a number of impressive outcomes in mouse models and clinical settings. In this study, we report that a timed triple immunotherapy (TTI) protocol using 3 agonist antibodies (anti-CD25mAb, anti-TGF-βmAb, and anti-CTLA-4mAb) produced complete clearance of established AB1 murine mesothelioma tumors. Combining all 3 agonist antibodies into a single cocktail for intratumoral injection was as effective as the TTI in tumor eradication. Cured mice showed elevated levels of tumor-specific IgG antibodies at 95 days posttreatment. Time-course studies of tumor clearance showed (1) that IgG levels were not elevated during tumor clearance and (2) that B-cell numbers were increased in the tumor-draining lymph nodes and spleens during tumor clearance. Finally, employment of B-cell knockout mice indicated a significant role for B cells in the successful eradication of the established tumors by the triple immunotherapy cocktail.
Krishnan, S., Bakker, M., Lee, C., Kissick, H., Ireland, D., & Beilharz, M. (2015). Successful combined intratumoral immunotherapy of established murine mesotheliomas requires B-Cell Involvement. Journal of Interferon and Cytokine Research, 35(2), 100-107. https://doi.org/10.1089/jir.2014.0054