CEACAM Immune Checkpoint Molecule for Drug Development

CEACAM (Carcinoembryonic Antigen Cell Adhesion Molecule) is a group of cell adhesion molecules that act as regulators in critical cellular processes and serve as characteristic tumor markers. At Creative Biolabs, we aim to provide comprehensive information and technical support on CEACAM immune checkpoints, enabling a deeper understanding of these crucial molecules in cancer immunotherapy.

Background and Structure of CEACAMs

CEACAM’s function in immune systems. (Dankner, et al., 2017) Fig 1. CEACAM's function in immune systems.¹

Belonging to the immunoglobulin superfamily adhesion molecules, CEACAMs comprise diverse proteins encoded by 12 genes located on human chromosome 19q13. Each CEACAM protein consists of an immunoglobulin variable domain (IgV) at its N-terminus, composed of 108 amino acids, and may contain 0-6 immunoglobulin constant domains (IgC). Notably, almost all observed CEACAM molecules are membrane-bound:

Linked by hydrophobic transmembrane structures: CEACAM1, CEACAM3, CEACAM4, CEACAM19, CEACAM20, and CEACAM21.
Linked by glycosylphosphatidylinositol (GPI): CEACAM5, CEACAM6, CEACAM7, CEACAM8.

Key CEACAM Proteins

Among the numerous CEACAM proteins identified, CEACAM1, as one of the earliest discovered proteins, has been extensively studied. Additionally, several other CEACAM proteins have emerged as key players:

Key Members	Names	Source	Functions
CEACAM1	BGP, CD66a	Granulocytes, Epithelial cells	In addition to participating in activation and phagocytosis, CEACAM1 also delays cell apoptosis.
CEACAM3	CGM1, CD66d	Granulocytes	Upon binding with bacterial Opa protein, CEACAM3 activates neutrophils and initiates phagocytosis.
CEACAM4	CGM7	Granulocytes	CEACAM4 stimulates the adhesion between neutrophils and endothelial cells.
CEACAM5	CEA, CD66e	Epithelial cells	CEA possesses strong chemotactic activity, which may induce and/or activate neutrophil adhesion.
CEACAM6	CGM6, CD66c	Granulocytes, Epithelial cells	In addition to participating in activation and phagocytosis, CEACAM6 also delays cell apoptosis.
CEACAM7	CGM2	Epithelial cells	Regulates the differentiation of normal cells and interacts with CEACAM1.
CEACAM8	CGM8, CD66b	Granulocytes	CEACAM8 stimulates the adhesion between neutrophils and endothelial cells.

Expression and Function of CEACAM

Under physiological conditions, CEACAM predominantly engages in homophilic interactions with adjacent cells, initiating signal transduction processes. These proteins are widely expressed in granulocytes and epithelial cells, regulating vital signaling events:

Granulocytes: CEACAM1, 3, 4, 6, and 8 expressed on neutrophils contribute to crucial functions. Their activities are modulated through molecular dimerization or cytoplasmic domain phosphorylation, affecting intracellular calcium ion concentration.
Epithelial Cells: Human CEACAM1, 5, and 6 are prevalent in various epithelial cells and derived cancers, finely tuning essential cellular behaviors.

CEACAMs. (Tchoupa, et al., 2014) Fig 2. CEACAMs.²

CEACAM Immune Checkpoints and Diseases

Several key CEACAM molecules have been identified as critical cancer markers or receptors for specific bacteria.

CEACAM1 has been found in melanoma, colorectal cancer, non-small cell lung cancer, pancreatic cancer, and bladder cancer.
CEACAM5 is widely used as a marker for the progression of colorectal malignant tumors.
CEACAM6 is expressed in breast cancer, pancreatic cancer, mucinous ovarian cancer, gastric cancer, and lung adenocarcinoma.
CEACAM3 participates in complement-dependent phagocytosis.
Certain pathogens use CEACAM1, 3, 5, and 6 to enhance their mucosal surface colonization ability.

CEACAM Immune Therapy

The extensive involvement of CEACAM molecules in cancer and their regulatory abilities in T/NK cell behaviors make them not only common broad-spectrum tumor markers but also potential and capable targets for cancer treatment. In recent years, clinical studies on CEACAM-targeted tumor immunotherapy have emerged, including:

Antibody-drug conjugates (ADC) targeting CEACAM5 (DM4 conjugates).
Bispecific antibodies (BsAb) used for radioimmunotherapy and imaging.
Anti-cancer activity-enhancing mAbs blocking the interaction between CEACAM1 and CEACAM5.
CAR-T therapy targeting CEACAM5.

Our Services

At Creative Biolabs, our unwavering commitment to technological advancement sets us apart from the rest. Our team of highly skilled experts possess an unparalleled depth of knowledge and expertise in the field of immune checkpoints. We continuously push the boundaries of innovation to deliver state-of-the-art solutions that meet the evolving needs of our clients.

We are committed to providing cutting-edge technology and expertise to advance your understanding and research in the field of CEACAM immune checkpoints. Contact us now to explore the full potential of CEACAM in cancer immunotherapy.

References

Dankner, et al. "CEACAM1 as a multi-purpose target for cancer immunotherapy." Oncoimmunology. 6.7 (2017): e1328336.
Tchoupa, et al. "Signaling by epithelial members of the CEACAM family – mucosal docking sites for pathogenic bacteria." Cell Communication and Signaling. 12 (2014): 27.

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