Successful combined intratumoral immunotherapy of established murine mesotheliomas requires B-Cell Involvement

Shruti Krishnan, Milly Bakker, C. Lee, Haydn Kissick, Demelza Ireland, Manfred Beilharz

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

© 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.
Original languageEnglish
Pages (from-to)100-107
JournalJournal of Interferon and Cytokine Research
Volume35
Issue number2
DOIs
Publication statusPublished - 2015

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