Tumor endothelial marker 1-specific DNA vaccination targets tumor vasculature

Tumor endothelial marker 1 (TEM1; also known as endosialin or CD248) is a protein found on tumor vasculature and in tumor stroma. Here, we tested whether TEM1 has potential as a therapeutic target for cancer immunotherapy by immunizing immunocompetent mice with Teml cDNA fused to the minimal domain...

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Bibliographic Details
Published in:The Journal of clinical investigation 2014-04, Vol.124 (4), p.1497
Main Authors: Facciponte, John G, Ugel, Stefano, De Sanctis, Francesco, Li, Chunsheng, Wang, Liping, Nair, Gautham, Sehgal, Sandy, Raj, Arjun, Matthaiou, Efthymia, Coukos, George, Facciabene, Andrea
Format: Article
Language:English
Subjects:
Blood-vessels
DNA vaccines
Immunotherapy
Neovascularization
Tumor markers
Tumors
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Summary:Tumor endothelial marker 1 (TEM1; also known as endosialin or CD248) is a protein found on tumor vasculature and in tumor stroma. Here, we tested whether TEM1 has potential as a therapeutic target for cancer immunotherapy by immunizing immunocompetent mice with Teml cDNA fused to the minimal domain of the C fragment of tetanus toxoid (referred to herein as Tem1-TT vaccine). Tem1-TT vaccination elicited [CD8.sup.+] and/or [CD4.sup.+] T cell responses against immunodominant TEM1 protein sequences. Prophylactic immunization ofanimals with Tem1-TT prevented or delayed tumor formation in several murine tumor models. Therapeutic vaccination of tumor-bearing mice reduced tumor vascularity, increased infiltration of [CD3.sup.+] T cells into the tumor, and controlled progression of established tumors. Tem1-TT vaccination also elicited [CD8.sup.+] cytotoxic T cell responses against murine tumor-specific antigens. Effective Tem1-TT vaccination did not affect angiogenesis-dependent physiological processes, including wound healing and reproduction. Based on these data and the widespread expression of TEM1 on the vasculature of different tumor types, we conclude that targeting TEM1 has therapeutic potential in cancer immunotherapy.
ISSN:0021-9738
1558-8238
DOI:10.1172/JCI67382.