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The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

mTOR Inhibition Improves Antitumor Effects of Vaccination with Antigen-Encoding RNA

Diken, Mustafa, Kreiter, Sebastian, Vascotto, Fulvia, Selmi, Abderraouf, Attig, Sebastian, Diekmann, Jan, Huber, Christoph, Türeci, Özlem, Sahin, Ugur·2013·Cancer Immunology Research
DOI 10.1158/2326-6066.cir-13-0046

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Abstract

Vaccination with in vitro transcribed RNA encoding tumor antigens is an emerging approach in cancer immunotherapy. Attempting to further improve RNA vaccine efficacy, we have explored combining RNA with immunomodulators such as rapamycin. Rapamycin, the inhibitor of mTOR, was used originally for immunosuppression. Recent reports in mouse systems, however, suggest that mTOR inhibition may enhance the formation and differentiation of the memory CD8+ T-cell pool. Because memory T-cell formation is critical to the outcome of vaccination aproaches, we studied the impact of rapamycin on the in vivo primed RNA vaccine-induced immune response using the chicken ovalbumin-expressing B16 melanoma model in C57BL/6 mice. Our data show that treatment with rapamycin at the effector-to-memory transition phase skews the vaccine-induced immune response toward the formation of a quantitatively and qualitatively superior memory pool and results in a better recall response. Tumor-infiltrating immune cells from these mice display a favorable ratio of effector versus suppressor cell populations. Survival of mice treated with the combined regimen of RNA vaccination with rapamycin is significantly longer (91.5 days) than that in the control groups receiving only one of these compounds (32 and 46 days, respectively). Our findings indicate that rapamycin enhances therapeutic efficacy of antigen-specific CD8+ T cells induced by RNA vaccination, and we propose further clinical exploration of rapamycin as a component of immunotherapeutic regimens. Cancer Immunol Res; 1(6); 386–92. ©2013 AACR.

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Citations

Cites

Research works printed but not linked: 17

  1. Kreiter, 2011, Tumor vaccination using messenger RNA: prospects of a future therapy, Curr Opin Immunol, 23, 399, 10.1016/j.coi.2011.03.007 · DOI
  2. Van, 2013 4, mRNA: From a chemical blueprint for protein production to an off-the-shelf therapeutic, Hum Vaccin Immunother., [Epub ahead of print]
  3. Diken, 2011, Selective uptake of naked vaccine RNA by dendritic cells is driven by macropinocytosis and abrogated upon DC maturation, Gene Ther, 18, 702, 10.1038/gt.2011.17 · DOI
  4. Scheel, 2006, Therapeutic anti-tumor immunity triggered by injections of immunostimulating single-stranded RNA, Eur J Immunol, 36, 2807, 10.1002/eji.200635910 · DOI
  5. Van, 2012, Preclinical evaluation of TriMix and antigen mRNA-based antitumor therapy, Cancer Res, 72, 1661, 10.1158/0008-5472.CAN-11-2957 · DOI
  6. Kreiter, 2008, Increased antigen presentation efficiency by coupling antigens to MHC class I trafficking signals, J Immunol, 180, 309, 10.4049/jimmunol.180.1.309 · DOI
  7. Kreiter, 2011, FLT3 ligand enhances the cancer therapeutic potency of naked RNA vaccines, Cancer Res, 71, 6132, 10.1158/0008-5472.CAN-11-0291 · DOI · Paper page
  8. Araki, 2010, The role of mTOR in memory CD8 T-cell differentiation, Immunol Rev, 235, 234, 10.1111/j.0105-2896.2010.00898.x · DOI
  9. Hackstein, 2002, Rapamycin inhibits macropinocytosis and mannose receptor-mediated endocytosis by bone marrow-derived dendritic cells, Blood, 100, 1084, 10.1182/blood.V100.3.1084 · DOI
  10. Li, 2012, Regulating mammalian target of rapamycin to tune vaccination-induced CD8(+) T cell responses for tumor immunity, J Immunol, 188, 3080, 10.4049/jimmunol.1103365 · DOI
  11. Wang, 2011, Temsirolimus, an mTOR inhibitor, enhances anti-tumour effects of heat shock protein cancer vaccines, Br J Cancer, 104, 643, 10.1038/bjc.2011.15 · DOI
  12. DuPage, 2012, Expression of tumour-specific antigens underlies cancer immunoediting, Nature, 482, 405, 10.1038/nature10803 · DOI
  13. Smyth, 2000, Differential tumor surveillance by natural killer (NK) and NKT cells, J Exp Med, 191, 661, 10.1084/jem.191.4.661 · DOI
  14. Zhong, 2000, Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics, Cancer Res, 60, 1541
  15. Gabrilovich, 1998, Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo, Blood, 92, 4150, 10.1182/blood.V92.11.4150 · DOI · Paper page
  16. Strauss, 2007, Selective survival of naturally occurring human CD4+CD25+Foxp3+ regulatory T cells cultured with rapamycin, J Immunol, 178, 320, 10.4049/jimmunol.178.1.320 · DOI
  17. Battaglia, 2005, Rapamycin selectively expands CD4+CD25+FoxP3 +regulatory T cells, Blood, 105, 4743, 10.1182/blood-2004-10-3932 · DOI

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Metadata

Authors
Diken, M., Kreiter, S., Vascotto, F., Selmi, A., Attig, S., Diekmann, J., Huber, C., Türeci, Ö., & Sahin, U.
Affiliations
Authors' Affiliations: 1TRON-Translational Oncology and 2Department of Internal Medicine III, University Medical Center of Johannes Gutenberg University; 3Ribological, Biontech AG; and 4Ganymed Pharmaceuticals, Mainz, Germany
Venue
Cancer Immunology Research
Publisher
American Association for Cancer Research (AACR)
Published
2013-12-01
Volume
1
Issue
6
Pages
386-392
ISSN
  • 2326-6066
  • 2326-6074
DOI
10.1158/2326-6066.cir-13-0046
Cited by
45
References
8
Language
en

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