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 and a member of the immunoglobulin superfamily.1

  • Under normal conditions, CEA is expressed at low levels on the apical surface of epithelial cells and may function as an adhesion molecule1-3
  • In cancer, CEA is overexpressed on the cell surface of a variety of tumor types, including colorectal, non-small cell lung, breast, pancreatic, and gastric cancers1-3

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.4

  • 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 activity.5-7

  • 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 bed6,7

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. 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
  3. 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.
  4. Davis MM. A new trigger for T cells. Cell. 2002;110:285-287. PMID: 12176315
  5. 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
  6. 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
  7. 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