EpCAM

The human epithelial cell adhesion molecule (EpCAM, CD326, Trop1) is a transmembrane, 40 kDa glycoprotein highly abundant in almost all human carcinomas, including colon, prostate, ovarian, or breast cancer [1]. In healthy tissue, EpCAM expression is generally low [1-2]. In cancer, EpCAM overexpression is responsible for tumor proliferation, invasion, and migration and is often correlated with a poor prognosis [1]. Thus, EpCAM represents an attractive therapeutic target. The number of EpCAM-positive cancers with limited therapeutic options at the advanced stage formed the rationale for developing the EpCAM/CD3 BiTE® antibody solitomab (MT110, AMG 110) [1].

CD3

The cluster of differentiation 3 (CD3, formerly named T3) is a multimeric protein complex consisting of four polypeptides (CD3ε, CD3γ, CD3δ, and CD3ζ) that assemble as three dimers (εγ, εδ, and ζζ) [4]. It is a marker of T cells, which recognizes and participates in the elimination of infected cells and tumor cells through the interaction between the TCR (T cell receptor) on T cells and the MHC-peptide complex on antigen-presenting cells [4-5]. Because of its short cytoplasmic tail, the TCR lacks the ability to signal and requires non-covalent association with the CD3. Upon antigen recognition, T cells' TCR/CD3 complex triggers downstream intracellular signaling and activates T cell cells [4].

References:

1. Brischwein K, et al., 2006. MT110: a novel bispecific single-chain antibody construct with high efficacy in eradicating established tumors. Mol Immunol. 43(8):1129-43.
2. Kebenko M, et al., 2018. A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refractory solid tumors. Oncoimmunology. 7(8):e1450710.
3. Chetty R. & Gatter K., 1994. CD3: structure, function, and role of immunostaining in clinical practice. J. Pathol. 173(4):303-307.
4. Smith-Garvin J.E. et al., 2009. T Cell Activation. Ann. Rev. Immunol. 27:591-619.3.

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