Enhanced therapeutic anti-tumor immunity induced by co-administration of 5-fluorouracil and adenovirus expressing CD40 ligand

Cancer Immunology, Immunotherapy : CII
L LiljenfeldtAristides G Eliopoulos

Abstract

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...Continue Reading

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Citations

Jan 3, 2016·Current Opinion in Immunology·Alistair M CookRichard A Lake
May 6, 2015·Oncoimmunology·Oliver KeppLorenzo Galluzzi
Apr 7, 2015·Cancer Treatment Reviews·Ghada S HassanWalid Mourad
Jan 9, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Emma ErikssonAngelica Loskog
Feb 28, 2020·Experimental and Therapeutic Medicine·Zhongxin Feng, Qi Chen
Mar 25, 2019·Cancer Immunology, Immunotherapy : CII·Constantin N BaxevanisSonia A Perez
Dec 25, 2019·Current Opinion in Biotechnology·Erkko Ylösmäki, Vincenzo Cerullo
Apr 4, 2021·International Journal of Molecular Sciences·Lorella TripodiLucio Pastore

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