CEA CD3 TCB

(RG7802, RO6958688)

Image: CEA CD3 TCB, a T-cell bispecific antibody
Breast
  • Phase
  • I
  • II
  • III
Gastrointestinal
  • Phase
  • I
  • II
  • III
Genitourinary
  • Phase
  • I
  • II
  • III
Gynecologic
  • Phase
  • I
  • II
  • III
Hematologic
  • Phase
  • I
  • II
  • III
Lung
  • Phase
  • I
  • II
  • III
Melanoma
  • Phase
  • I
  • II
  • III
Solid Tumor
  • Phase
  • I
  • II
  • III

This compound and its uses are investigational and have not been approved by the US Food and Drug Administration. Efficacy and safety have not been established. The information presented should not be construed as a recommendation for use. The relevance of findings in preclinical studies to humans is currently being evaluated.

CEA CD3 TCB, a T-cell bispecific (TCB) antibody

CEA CD3 TCB is a novel, investigational, immunoglobulin G1 (IgG1) T-cell bispecific (TCB) antibody developed to engage the immune system against cancer. CEA CD3 TCB is designed to redirect the activity of T cells to tumor cells by simultaneously binding to the CD3 epsilon (CD3ε) chain found on T cells and carcinoembryonic antigen (CEA), a tumor surface antigen.1 Having 2 copies (bivalent) of the CEA-recognizing region, CEA CD3 TCB is designed to increase the affinity for binding to CEA-expressing tumors. Its monovalent CD3ε binding domain is intended to facilitate CD3 binding and, upon binding to CEA-expressing tumor cells, to enable T-cell activation. Engagement of T cells by CEA CD3 TCB is independent of their specificity and activation status. Engineered Fc region (P329G LALA mutation) may result in an extended half-life.1,2

CEA CD3 TCB crosslinks T cells to tumor cells, which may lead to the activation of the CD3 downstream signaling pathway and formation of immunologic synapses. Introduction of CEA CD3 TCB is believed to lead to T-cell recruitment and/or intratumor T-cell expansion/proliferation, thus converting the noninflamed tumors into highly inflamed tumors, resulting in the generation of an inflamed tumor microenvironment.1

1 CEA CD3 TCB (RG7802, RO6958688) is an investigational IgG1 TCB antibody currently being studied for its potential to bind CD3 on T cells to CEA-expressing tumors.1

Image: CEA-expressing tumor cells

2 CEA CD3 TCB is designed to redirect T cells to tumor cells by simultaneously binding to the CD3ε chain found on T cells and CEA, a tumor surface antigen.1

Image: CEA CD3 TCB, CEA-expressing tumor cell, and CD3 on T cell

3 Preclinical data have shown that CEA CD3 TCB demonstrated antitumor activity in poorly infiltrated tumors, and thus has the potential to convert noninflamed tumors into inflamed tumors. CEA CD3 TCB continues to be investigated in ongoing clinical studies.1

Image: T cell and CEA CD3 TCB

References

  1. 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
  2. Lehmann S, Perera R, Grimm HP, 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