p95 Human epidermal growth factor receptor 2 (p95HER2)-Cluster of differentiation 3 epsilon (CD3e) complex (p95HER2-CD3)

p95HER2 is a carboxy-terminal fragment of the Human Epidermal Growth Factor Receptor 2 (HER2) that lacks the extracellular domain, which is the binding site for standard HER2-targeted therapies like trastuzumab (Arribas et al., 2011). The p95HER2-CD3 synapse refers to the immunological bridge formed by bispecific antibodies that simultaneously bind to p95HER2 on tumor cells and the CD3 epsilon subunit on T cells (Rius Ruiz et al., 2018). This interaction facilitates the recruitment and activation of cytotoxic T lymphocytes (CTLs) directly at the tumor site, bypassing the need for traditional antigen presentation. By targeting p95HER2, these therapies specifically address a subset of HER2-positive cancers that are often more aggressive and treatment-resistant (Parra-Palau et al., 2014). The formation of this synapse leads to the release of perforins and granzymes, resulting in the lysis of the p95HER2-expressing cancer cells. This approach is particularly valuable because p95HER2 is highly tumor-specific, potentially reducing off-target effects on healthy tissues that express full-length HER2 (Rius Ruiz et al., 2018).

Other names

p95HER2-CD3 immunological synapsep95HER2/CD3p95HER2-TCB target611-CTF HER2-CD3 complexTruncated HER2-CD3 epsilon interaction

T-cell redirection and activation via bispecific antibody binding to tumor-specific p95HER2 and T-cell CD3 epsilon