Synergy between chemotherapeutic agents and CTLA-4 blockade in preclinical tumor modelsReport as inadecuate




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Cancer Immunology, Immunotherapy

, Volume 62, Issue 9, pp 1533–1545

First Online: 20 July 2013Received: 02 January 2013Accepted: 06 June 2013DOI: 10.1007-s00262-013-1451-5

Cite this article as: Jure-Kunkel, M., Masters, G., Girit, E. et al. Cancer Immunol Immunother 2013 62: 1533. doi:10.1007-s00262-013-1451-5

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.

KeywordsChemotherapy CTLA-4 Preclinical Synergy Tumor model  Download fulltext PDF



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

Source: https://link.springer.com/



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