MilliporeSigma
  • Tumor endothelial marker 1-specific DNA vaccination targets tumor vasculature.

Tumor endothelial marker 1-specific DNA vaccination targets tumor vasculature.

The Journal of clinical investigation (2014-03-20)
John G Facciponte, Stefano Ugel, Francesco De Sanctis, Chunsheng Li, Liping Wang, Gautham Nair, Sandy Sehgal, Arjun Raj, Efthymia Matthaiou, George Coukos, Andrea Facciabene
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Dextran sulfate sodium salt from Leuconostoc spp., for molecular biology, average Mw >500,000 (dextran starting material), contains 0.5-2% phosphate buffer
Roche
In Situ Cell Death Detection Kit, AP, sufficient for ≤50 tests, kit of 1 (3 components), suitable for detection