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

CEA image: CEA, a transmembrane protein expressed on tumor cells

Carcinoembryonic antigen (CEA) is a cell-surface protein that mediates intracellular adhesion.1

  • In normal epithelial tissues, CEA is expressed at low levels and in an orientation that is not easily bound by therapeutic antibodies2,3
  • In cancer, CEA bridges healthy cells and tumor cells, which may play a role in metastasis4
  • CEA is highly expressed in multiple tumor types, including colorectal, gastric, pancreatic, non-small cell lung, breast, and other cancers1,2,5

CD3: a T-cell activator

CD3 image: CD3, a protein on the surface of T cells

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

CEA CD3 image: CEA on tumor cell and CD3 on T cell

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 activity3,7,8

  • 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

  1. 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
  2. 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.
  3. Bacac M, Klein C, Umana P. CEA TCB: a novel head-to-tail 2:1 T cell bispecific antibody for treatment of CEA-positive solid tumors. Oncoimmunology. 2016;5:e1203498. PMID: 27622073
  4. 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
  5. 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
  6. 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
  7. Bacac M, Fauti T, Sam J, et al. A novel carcinoembryonic antigen T-cell bispecific antibody (CEA TCB) for the treatment of solid tumors. Clin Cancer Res. 2016;22:3286-3297. PMID: 26861458
  8. Lehmann S, Perera R, Grimm H-P, et al. In vivo fluorescence imaging of the activity of CEA TCB, a novel T-cell bispecific antibody, reveals highly specific tumor targeting and fast induction of T-cell–mediated tumor killing. Clin Cancer Res. 2016;22:4417-4427. PMID: 27117182