Tumor vasculature and stroma-associated HLA-A*02:01-restricted peptides

This target represents a specific panel of HLA-A*02:01-restricted peptides derived from six proteins: Delta-like 1 homolog (DLK1), Ephrin type-A receptor 2 (EPHA2), Hemoglobin subunit beta (HBB), Neuropilin-1 (NRP1), Regulator of G-protein signaling 5 (RGS5), and Tumor endothelial marker 1 (TEM1/CD248). These proteins are significantly overexpressed in the tumor microenvironment, particularly within the vasculature (endothelial cells and pericytes) and the supporting stroma (fibroblasts) (Walter et al., 2012; UniProt). By targeting these non-malignant but essential components of the tumor infrastructure, therapeutic strategies aim to disrupt angiogenesis and the physical support system of the tumor, which may be less prone to the genetic instability and heterogeneity seen in tumor cells (Immatics Biotechnologies). These peptides are typically delivered as part of multi-peptide vaccines, such as IMA941 for renal cell carcinoma and IMA910 for colorectal cancer, to stimulate a robust cytotoxic T-cell response (ClinicalTrials.gov NCT00666172). The therapeutic goal is to induce the immune system to recognize and destroy cells presenting these antigens, thereby inhibiting tumor growth and improving patient survival. This approach is currently being evaluated in various clinical trials for solid tumors where the stroma plays a critical role in disease progression.

Other names

Tumor vasculature and stromal cells expressing DLK1, EPHA2, HBB, NRP1, RGS5, and TEM1-derived peptides in HLA-A*02:01Tumor-associated peptides (TUMAPs)Tumor vasculature antigens (TVAs)Stroma-associated antigensIMA941/IMA910 peptide components

Induction of peptide-specific CD8+ T-cell responses against tumor vasculature and stromal cells (Walter et al., 2012).