TY - JOUR
T1 - Successful combined intratumoral immunotherapy of established murine mesotheliomas requires B-Cell Involvement
AU - Krishnan, Shruti
AU - Bakker, Milly
AU - Lee, C.
AU - Kissick, Haydn
AU - Ireland, Demelza
AU - Beilharz, Manfred
PY - 2015
Y1 - 2015
N2 - © 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.
AB - © 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.
UR - https://www.scopus.com/pages/publications/84922505826
U2 - 10.1089/jir.2014.0054
DO - 10.1089/jir.2014.0054
M3 - Article
C2 - 25259549
SN - 1079-9907
VL - 35
SP - 100
EP - 107
JO - Journal of Interferon and Cytokine Research
JF - Journal of Interferon and Cytokine Research
IS - 2
ER -
