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

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

Research output: Contribution to journalArticle

22 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1461-1472
Number of pages12
JournalCancer Immunology, Immunotherapy
Volume60
Issue number10
DOIs
StatePublished - Oct 1 2011
Externally publishedYes

Fingerprint

Myxoma virus
Sirolimus
Cell- and Tissue-Based Therapy
Brain Neoplasms
Melanoma
T-Lymphocytes
Neoplasms
Adoptive Transfer
Therapeutics
Oncolytic Viruses
Viruses
Adoptive Immunotherapy
Neutralizing Antibodies
Safety
Peptides
Injections
Brain
Infection

Keywords

  • Brain tumor
  • Melanoma
  • Myxoma virus
  • Rapamycin
  • T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

Cite this

Myxoma virus combined with rapamycin treatment enhances adoptive T cell therapy for murine melanoma brain tumors. / Thomas, Diana L.; Doty, Rosalinda; Tosic, Vesna; Liu, Jia; Kranz, David M.; McFadden, Douglas; MacNeill, Amy L.; Roy, Edward J.

In: Cancer Immunology, Immunotherapy, Vol. 60, No. 10, 01.10.2011, p. 1461-1472.

Research output: Contribution to journalArticle

Thomas, Diana L. ; Doty, Rosalinda ; Tosic, Vesna ; Liu, Jia ; Kranz, David M. ; McFadden, Douglas ; MacNeill, Amy L. ; Roy, Edward J. / Myxoma virus combined with rapamycin treatment enhances adoptive T cell therapy for murine melanoma brain tumors. In: Cancer Immunology, Immunotherapy. 2011 ; Vol. 60, No. 10. pp. 1461-1472.
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