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Open Access 01-09-2013 | Original Article

Synergy between chemotherapeutic agents and CTLA-4 blockade in preclinical tumor models

Authors: Maria Jure-Kunkel, Gregg Masters, Emel Girit, Gennaro Dito, Francis Lee, John T. Hunt, Rachel Humphrey

Published in: Cancer Immunology, Immunotherapy | Issue 9/2013

Abstract

Ipilimumab, a cytotoxic T-lymphocyte antigen-4 (CTLA-4) binding agent, has proven to be an effective monotherapy for metastatic melanoma and has shown antitumor activity in trials when administered with other therapeutic agents. We hypothesized that the combination of ipilimumab with chemotherapeutic agents, such as ixabepilone, paclitaxel, etoposide, and gemcitabine, may produce therapeutic synergy based on distinct but complementary mechanisms of action for each drug and unique cellular targets. This concept was investigated using a mouse homolog of ipilimumab in preclinical murine tumor models, including SA1N fibrosarcoma, EMT-6 mammary carcinoma, M109 lung carcinoma, and CT-26 colon carcinoma. Results of CTLA-4 blockade in combination with one of various chemotherapeutic agents demonstrate that synergy occurs in settings where either agent alone was not effective in inducing tumor regression. Furthermore, when combined with CTLA-4 blockade, ixabepilone, etoposide, and gemcitabine elicited prolonged antitumor effects in some murine models with induction of a memory immune response. Future investigations are warranted to determine which specific chemo-immunotherapy combinations, if any, will produce synergistic antitumor effects in the clinical setting.

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Title: Synergy between chemotherapeutic agents and CTLA-4 blockade in preclinical tumor models
Authors: Maria Jure-Kunkel
Gregg Masters
Emel Girit
Gennaro Dito
Francis Lee
John T. Hunt
Rachel Humphrey
Publication date: 01-09-2013
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 9/2013
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-013-1451-5

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