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01-10-2011 | Original article

Myxoma virus combined with rapamycin treatment enhances adoptive T cell therapy for murine melanoma brain tumors

Authors: Diana L. Thomas, Rosalinda Doty, Vesna Tosic, Jia Liu, David M. Kranz, Grant McFadden, Amy L. MacNeill, Edward J. Roy

Published in: Cancer Immunology, Immunotherapy | Issue 10/2011

Abstract

Adoptive transfer of tumor-specific T cells has shown some success for treating metastatic melanoma. We evaluated a novel strategy to improve adoptive therapy by administering both T cells and oncolytic myxoma virus to mice with syngeneic B16.SIY melanoma brain tumors. Adoptive transfer of activated CD8⁺ 2C T cells that recognize SIY peptide doubled survival time, but SIY-negative tumors recurred. Myxoma virus killed B16.SIY cells in vitro, and intratumoral injection of virus led to selective and transient infection of the tumor. Virus treatment recruited innate immune cells to the tumor and induced IFNβ production in the brain, resulting in limited oncolytic effects in vivo. To counter this, we evaluated the safety and efficacy of co-administering 2C T cells, myxoma virus, and either rapamycin or neutralizing antibodies against IFNβ. Mice that received either triple combination therapy survived significantly longer with no apparent side effects, but eventually relapsed. Importantly, rapamycin treatment did not impair T cell-mediated tumor destruction, supporting the feasibility of combining adoptive immunotherapy and rapamycin-enhanced virotherapy. Myxoma virus may be a useful vector for transient delivery of therapeutic genes to a tumor to enhance T cell responses.

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Title: Myxoma virus combined with rapamycin treatment enhances adoptive T cell therapy for murine melanoma brain tumors
Authors: Diana L. Thomas
Rosalinda Doty
Vesna Tosic
Jia Liu
David M. Kranz
Grant McFadden
Amy L. MacNeill
Edward J. Roy
Publication date: 01-10-2011
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 10/2011
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-011-1045-z

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