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Tumor endothelial marker 1–specific DNA vaccination targets tumor vasculature
John G. Facciponte, … , George Coukos, Andrea Facciabene
John G. Facciponte, … , George Coukos, Andrea Facciabene
Published March 18, 2014
Citation Information: J Clin Invest. 2014;124(4):1497-1511. https://doi.org/10.1172/JCI67382.
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Research Article Oncology Article has an altmetric score of 77

Tumor endothelial marker 1–specific DNA vaccination targets tumor vasculature

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Abstract

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 Tem1 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+ and/or CD4+ T cell responses against immunodominant TEM1 protein sequences. Prophylactic immunization of animals 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+ T cells into the tumor, and controlled progression of established tumors. Tem1-TT vaccination also elicited CD8+ 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.

Authors

John G. Facciponte, Stefano Ugel, Francesco De Sanctis, Chunsheng Li, Liping Wang, Gautham Nair, Sandy Sehgal, Arjun Raj, Efthymia Matthaiou, George Coukos, Andrea Facciabene

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Figure 6

Wound healing is not delayed by Tem1-TT immunization.

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Wound healing is not delayed by Tem1-TT immunization.
(A) Time course of...
(A) Time course of wound healing. C57BL/6 mice were vaccinated 5 times with Tem1-TT or TT vaccine. 10 days after the final vaccination, 2 circular wounds were inflicted on the upper back of the mice. The wound area was measured every 2 days. Data are mean ± SD of 2 experiments (n = 10 per group for each experiment). P = 0.726, Tem1-TT vs. TT, pairwise multiple-comparison Tukey test. (B and C) TEM1-specific response. 20 days after the punch biopsies, mice were sacrificed to check the immune response against TEM1 antigen by IFN-γ ELISpot (B) and ICS (C) of bulk splenocytes (1 × 106). Statistical analyses were performed with Student’s t test.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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