Explore CEA CD3
Simultaneous binding of CEA on tumor cells and CD3 on T cells activates T cells, resulting in T-cell–mediated tumor killing
CEA: a tumor surface antigen
Carcinoembryonic antigen (CEA) is a cell-surface protein that mediates intracellular adhesion.1
- CEA is expressed at low levels on the apical surface of normal epithelial tissues in a polarized expression pattern not accessible by therapeutic antibodies2
- In cancer, CEA bridges healthy cells and tumor cells, which may play a role in metastasis3
- CEA is highly expressed in multiple tumor types, including colorectal, gastric, pancreatic, non-small cell lung, breast, and other cancers1,4,5
CD3: a T-cell activator
CD3 (cluster of differentiation 3) is a multimeric protein composed of 4 subunits (γ, δ, ϵ, ζ), which are part of the T-cell receptor complex on the surface of T cells.6
- Engagement of CD3 induces downstream signaling events that result in T-cell activation
Potential of simultaneous binding of CEA and CD3
Binding of a T-cell bispecific antibody to CEA on tumor cells and CD3 on T cells engages T cells and redirects their activity against tumor cells. T-cell activation—a result of the CEA-CD3 interaction—promotes the proliferation/expansion of pre-existing T cells and the recruitment of new T cells from the peripheral blood to the tumor microenvironment, which may further contribute to antitumor activity.2
- In preclinical models, binding of T‑cell bispecific antibodies to CEA and CD3 induced tumor regression through T‑cell proliferation at tumor sites and recruitment of new T cells to the tumor bed7,8
References
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- Beauchemin N, Arabzadeh A. Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) in cancer progression and metastasis. Cancer Metastasis Rev. 2013;32:643-671. PMID: 23903773
- Bacac M, Klein C, Umana P. Oncoimmunology. 2016;5:e1203498. PMID: 27622073
- Dallas MR, Liu G, Chen W-C, et al. Divergent roles of CD44 and carcinoembryonic antigen in colon cancer metastasis. FASEB J. 2012;26:2648-2656. PMID: 22415308
- Morse MA, Clay TM,
Lyerly HK. Tumor antigens. In: Kaufman HL, Wolchok JD, eds.
General Principles of Tumor Immunotherapy. Dordrecht, The
Netherlands: Springer; 2007:23.
- Hammarström S. The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin Cancer Biol. 1999;9:67-81. PMID: 10202129
- Borroto A, Arellano I, Blanco R, et al. Relevance of Nck-CD3ε interaction for T cell activation in vivo. J Immunol. 2014;192:2042-2053. PMID: 24470497
- Bacac M, Fauti T, Sam J, et al. Clin Cancer Res. 2016;22:3286-3297. PMID: 26861458
- Lehmann S, Perera R, Grimm H-P, et al. Clin Cancer Res. 2016;22:4417-4427.PMID: 27117182