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.
Cibisatamab is designed to engage T cells to kill tumor cells
Cibisatamab is a 2:1 T-cell bispecific (TCB) antibody that simultaneously binds to carcinoembryonic antigen (CEA) on tumor cells and CD3 on T cells. This design allows cibisatamab to selectively target tumors and induce T-cell mediated killing of CEA-expressing tumor cells.1 Bivalent CEA binding increases tumor targeting and retention as compared to primary cells. Binding to the membrane-proximal domain of CEA confers specificity to membrane-anchored CEA and prevents interaction with soluble CEA.1,2 Monovalent CD3 binding controls T-cell activation, which can only occur when cibisatamab is also bound to CEA-expressing tumor cells. This prevents activation in the peripheral blood, specifically in the absence of CEA-expressing tumors.1 Additional features of cibisatamab include a short flexible linker that enables tight connection between tumor cells and T cells, and a silent Fc region that provides an extended half-life and prevents binding to Fcγ receptor-expressing immune cells.1,2
The 2:1 bivalent design of cibisatamab enables selective T-cell
activation against CEA-expressing tumors, as shown in preclinical studies.1
1 Cibisatamab engages and activates T cells to induce tumor cell killing
In preclinical studies, cibisatamab 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 and chemokines that recruit additional T cells to the tumor site
By engaging T cells in the tumor microenvironment, cibisatamab could turn non-inflamed tumors into inflamed tumors.2
2 Combining cibisatamab with PD-L1 inhibition may maintain antitumor T-cell activity
As a means of immune evasion, tumor cells may overexpress PD-L1
following cibisatamab–mediated T-cell attack.2 When PD-L1
binds to PD-1 on T cells, T cells become deactivated.3
Blocking PD-L1 can help T cells remain activated against tumor cells.4
3 Combining cibisatamab with PD-L1 inhibition may amplify tumor-cell killing
Cibisatamab in combination with PD-L1 inhibition induces increased
T-cell activation and proliferation in the tumor microenvironment. As
a result, tumor-cell killing and propagation of antitumor immune
effects has the potential to create an inflamed, immunologically
active tumor microenvironment.1,2
CD=cluster of differentiation; CEA=carcinoembryonic antigen; Fc=fragment crystallizable; PD-1=programmed death-1; PD-L1=programmed death-ligand 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
- 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
- Chen DS, Mellman I.
Elements of cancer immunity and the cancer-immune set point.
Nature. 2017;541:321-330. PMID: 28102259
- 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