Human epidermal growth factor receptor 2 (HER2) and Carcinoembryonic antigen-related cell adhesion molecule 5 (CEA) (HER2 and CEA)

Human epidermal growth factor receptor 2 (HER2) and Carcinoembryonic antigen-related cell adhesion molecule 5 (CEA) are two distinct tumor-associated antigens that are frequently co-expressed in solid tumors such as breast, gastric, and colorectal cancers [1, 4]. HER2 is a member of the epidermal growth factor receptor family and acts as a receptor tyrosine kinase that drives cell proliferation and survival [4, 11]. CEA is a cell surface glycoprotein involved in cell adhesion and is often used as a clinical biomarker for disease progression [3, 7]. While they are separate proteins, they are often targeted together in combinatorial immunotherapy strategies, such as dual-component DNA vaccines (e.g., V932) and logic-gated CAR-T cells, to enhance tumor selectivity and reduce off-target effects [1, 12]. HER2-targeted therapies like trastuzumab are standard of care for HER2-positive cancers, while CEA-targeted agents like cibisatamab are being evaluated for their ability to redirect the immune system against CEA-expressing cells [9, 16]. The simultaneous assessment of HER2 and CEA levels is also clinically significant for monitoring treatment efficacy and predicting patient outcomes in metastatic settings [3, 5].

Other names

ERBB2CD340Proto-oncogene NeuCEACAM5Carcinoembryonic antigenCD66e

HER2-targeted drugs work by inhibiting receptor dimerization, blocking downstream signaling (MAPK/PI3K), and inducing antibody-dependent cell-mediated cytotoxicity (ADCC) [2, 16]. CEA-targeted therapies, such as bispecific T-cell engagers (TCBs), redirect T-cells to kill CEA-expressing tumor cells [9]. Dual-targeting strategies, including DNA vaccines (e.g., V932) and synNotch CAR-T systems, aim to activate the immune system against both antigens simultaneously to improve specificity and overcome resistance [1, 4].