Efficient eradication of subcutaneous but not of autochthonous gastric tumors by adoptive T cell transfer in an SV40 T antigen mouse model

The Journal of Immunology : Official Journal of the American Association of Immunologists
Carole BourquinStefan Endres

Abstract

In stomach cancer, there is a need for new therapeutic strategies, in particular for the treatment of unresectable tumors and micrometastases. We investigated the efficacy of immunotherapy in an autochthonous model of gastric cancer, the CEA424-SV40 T Ag (TAg) transgenic mice. Treatment efficacy against both the autochthonous tumors and s.c. tumors induced by the derived cell line mGC3 were assessed. In wild-type mice, a dendritic cell vaccine loaded with irradiated tumor cells combined with CpG oligonucleotides induced efficient cytotoxic T cell and memory responses against mGC3 s.c. tumors. In contrast, neither s.c. nor autochthonous tumors responded to vaccination in CEA424-SV40 TAg mice, indicating tolerance to the SV40 TAg. To examine whether tumors in these mice were principally accessible to immunotherapy, splenocytes from immune wild-type mice were adoptively transferred into CEA424-SV40 TAg transgenic mice. Treated mice showed complete regression of the s.c. tumors associated with intratumoral infiltrates of CD8 and CD4 T cells. In contrast, the autochthonous gastric tumors in the same mice were poorly infiltrated and did not regress. Thus, even in the presence of an active anti-tumoral T cell response, autochthonous g...Continue Reading

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Citations

Feb 15, 2013·Science Translational Medicine·Federico SandovalEric Tartour
Nov 27, 2014·Journal of the National Cancer Institute·Sebastian KoboldStefan Endres
Nov 27, 2014·Human Vaccines & Immunotherapeutics·Mevyn NizardEric Tartour
Oct 6, 2017·Oncotarget·Michael Bruns, Wolfgang Deppert
Sep 1, 2018·World Journal of Gastroenterology : WJG·Daniela Cornelia LazărAdrian Goldiș
Aug 31, 2018·Frontiers in Immunology·Masaki Terabe, Jay A Berzofsky
Aug 7, 2017·BioMed Research International·Mohamed AbozeidRoberta Sommaggio
Jan 1, 2021·Histopathology·Matthew W Rosenbaum, Raul S Gonzalez

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