Human epidermal growth factor receptor 2-derived E75 peptide-HLA complex (HER2 E75-HLA)

The Human epidermal growth factor receptor 2-derived E75 peptide-HLA complex is a specific molecular target used in cancer immunotherapy, consisting of a nine-amino acid sequence (KIFGSLAFL) from the extracellular domain of the HER2/neu protein (Mittendorf et al., 2008). This peptide is processed and presented on the surface of antigen-presenting cells and tumor cells by specific Human Leukocyte Antigen (HLA) class I molecules, including HLA-A2, A3, A24, and A26 (Peoples et al., 2005; Sears et al., 2011). The primary biological role of this complex is to serve as a signal for the immune system, specifically triggering the activation and proliferation of CD8+ cytotoxic T lymphocytes (CTLs). In the context of oncology, drugs like Nelipepimut-S (NeuVax) utilize this peptide to vaccinate patients against HER2-expressing tumors, particularly in breast cancer cases with low-to-intermediate HER2 expression (Brown et al., 2020). By mimicking the presentation of this antigen, the therapy induces a robust immune memory intended to prevent disease recurrence. Clinical application requires screening for both HER2 protein expression and compatible HLA types to ensure effective T-cell recognition. This target is particularly significant because it allows for the targeting of cells that may not have high enough HER2 levels for traditional monoclonal antibody therapies like trastuzumab. Research has shown that the E75 peptide is highly immunogenic and can elicit a sustained CTL response when administered with an adjuvant like GM-CSF.

Other names

E75 peptideNelipepimut-SHER2/neu (369-377)KIFGSLAFLNeuVaxHER2-derived peptide E75

Nelipepimut-S is a peptide vaccine that, when presented by HLA-A2, A3, A24, or A26 on antigen-presenting cells, induces a specific CD8+ cytotoxic T-lymphocyte response against HER2-expressing cells (Mittendorf et al., 2008).