Tumour eradication and induction of memory against murine mesothelioma by combined immunotherapy

Immunology and Cell Biology
Haydn T KissickManfred W Beilharz

Abstract

Numerous immunotherapy treatments for cancer are undergoing clinical trials or are already approved for use. One particular area of interest is targeting mechanisms of immune tolerance. Using a murine model of mesothelioma, we investigated the roles of regulatory T-cells, intratumoural transforming growth factor (TGF)-β and the negative regulator molecule cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) in immune tolerance to tumours. It was found that treatments targeting a single negative regulator molecule mechanism were not as effective against tumours as targeting multiple mechanisms simultaneously. Most importantly, it was found that a combined triple treatment of anti-CD25 monoclonal antibody (mAb), anti-CTLA-4 mAb and TGF-β soluble receptor resulted in long-term clearance of tumours and memory against tumour rechallenge. These data suggest that clinical application of immunotherapies against tumours may be improved by simultaneously targeting multiple mechanisms of immune suppression.

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Citations

Feb 4, 2012·Cancer Microenvironment : Official Journal of the International Cancer Microenvironment Society·Demelza J IrelandManfred W Beilharz
Oct 5, 2015·Cancer Treatment Reviews·Elly MarcqEvelien L J Smits
Aug 21, 2013·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Chindu GovindarajMagdalena Plebanski
Sep 27, 2014·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Shruti KrishnanManfred W Beilharz

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