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Enhanced therapeuti...
Enhanced therapeutic anti-tumor immunity induced by co-administration of 5-fluorouracil and adenovirus expressing CD40 ligand
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- Liljenfeldt, Lina (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
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- Gkirtzimanaki, Katerina (författare)
- University of Crete medical School, FORTH Hellas
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- Vyrla, Dimitra (författare)
- University of Crete medical School, FORTH Hellas
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- Svensson, Emma (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
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- Loskog, Angelica Si (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk immunologi
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- Eliopoulos, Aristides G (författare)
- University of Crete medical School, FORTH Hellas
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(creator_code:org_t)
- 2013-12-20
- 2014
- Engelska.
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Ingår i: Cancer Immunology and Immunotherapy. - : Springer Science and Business Media LLC. - 0340-7004 .- 1432-0851. ; 63:3, s. 273-282
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Bystander immune activation by chemotherapy has recently gained extensive interest and provided support for the clinical use of chemotherapeutic agents in combination with immune enhancers. The CD40 ligand (CD40L; CD154) is a potent regulator of the anti-tumor immune response and recombinant adenovirus (RAd)-mediated CD40L gene therapy has been effective in various cancer models and in man. In this study we have assessed the combined effect of local RAd-CD40L and 5-fluorouracil (5-FU) administration on a syngeneic MB49 mouse bladder tumor model. Whereas MB49 cells implanted into immunocompetent mice responded poorly to RAd-CD40L or 5-FU alone, administration of both agents dramatically decreased tumor growth, increased survival of the mice and induced systemic MB49-specific immunity. This combination treatment was ineffective in athymic nude mice, highlighting an important role for T cell mediated anti-tumor immunity for full efficacy. 5-FU up-regulated the expression of Fas and immunogenic cell death markers in MB49 cells and cytotoxic T lymphocytes from mice receiving RAd-CD40L immunotherapy efficiently lysed 5-FU treated MB49 cells in a Fas ligand-dependent manner. Furthermore, local RAd-CD40L and 5-FU administration induced a shift of myeloid-derived suppressor cell phenotype into a less suppressive population. Collectively, these data suggest that RAd-CD40L gene therapy is a promising adjuvant treatment to 5-FU for the management of bladder cancer.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- Oncology
- Onkologi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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