CEA-TCB

(RG7802)

CEA-TCB image: CEA-TCB, a 2:1 T-cell bispecific antibody
Breast
  • Phase
  • I
  • II
  • III
Gastrointestinal
  • Phase
  • I
  • II
  • III
Genitourinary
  • Phase
  • I
  • II
  • III
Gynecologic
  • Phase
  • I
  • II
  • III
Hematology
  • 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-TCB is designed for tumor selectivity

CEA-TCB is a 2:1 T-cell bispecific (TCB) antibody that bivalently binds to carcinoembryonic antigen (CEA) on tumor cells and monovalently binds to CD3 on T cells.1 Bivalent CEA binding increases specificity and retention to CEA on tumor cells and prevents activity toward CEA on normal cells and soluble CEA.1,2 Monovalent CD3 binding controls T-cell activation, which can occur when both CEA domains are bound. This prevents activation in the absence of CEA-expressing tumors.1 Additional features of CEA-TCB include a flexible linker that allows for simultaneous binding of CEA and CD3, and a fully silent Fc region that extends half-life and prevents activation of innate immune effector cells.1,2

The 2:1 bivalent design of CEA-TCB enables selective T-cell activation against CEA-expressing tumors, as shown in preclinical studies.1
 

1 CEA-TCB activates T cells to induce tumor cell killing

 

In preclinical studies, CEA-TCB binds simultaneously to T cells and tumor cells. This has the potential to increase2

  • The number of T cells in the tumor microenvironment
  • T-cell secretion of cytotoxic granules that cause tumor cell lysis
  • Release of cytokines that recruit additional T cells to the tumor site

By engaging T cells in the tumor microenvironment, CEA-TCB could turn non-inflamed tumors into inflamed tumors.2

CEA-TCB image: CEA-TCB activates T cells to induce tumor cell killing

 

2 Combining CEA-TCB with PD-L1 inhibition may maintain antitumor T-cell activity

 

Tumor cells may overexpress PD-L1 as a result of CEA-TCB–mediated T-cell attack. When PD-L1 binds to PD-1 on T cells, T cells become deactivated. Blocking PD-L1 can help T cells remain activated against tumor cells.2-4

CEA-TCB image: Combining CEA-TCB with PD-L1 inhibition may maintain antitumor T-cell activity

 

3 Combining CEA-TCB with PD-L1 inhibition may amplify tumor-cell killing

 

Combining CEA-TCB with PD-L1 inhibition may induce increased T-cell activation and proliferation in the tumor microenvironment. As a result, potent tumor killing and propagation of antitumor immune effects can create an inflamed, immunologically active tumor microenvironment.1,2,5-7

CEA-TCB image: Combining CEA-TCB with PD-L1 inhibition may amplify tumor-cell killing

 

PD-1=programmed death-1; PD-L1=programmed death-ligand 1.

References

  1. 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
  2. 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
  3. Chen DS, Irving BA, Hodi FS. Molecular pathways: next‐generation immunotherapy–inhibiting programmed death‐ligand 1 and programmed death‐1. Clin Cancer Res. 2012;18:6580-6587. PMID: 23087408
  4. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677-704. PMID: 18173375
  5. Kim JM, Chen DS. Immune escape to PD-L1/PD-1 blockade: seven steps to success (or failure). Ann Oncol. 2016;27:1492-1504. PMID: 27207108
  6. 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
  7. Topalian SL, Drake CG, Pardoll DM. Targeting the PD-1/B7-H1 (PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol. 2012;24:207-212. PMID: 22236695