CEA Human
Description
Biochemical Characteristics
CEA Human is a 72.3 kDa glycosylated polypeptide chain comprising 659 amino acids (35-685a.a.), expressed with an 8-amino-acid His tag at the C-terminus . Produced via recombinant technology in Sf9 Baculovirus cells, its molecular weight varies between 70-150 kDa on SDS-PAGE due to glycosylation . The protein contains a 45-60% carbohydrate component and anchors to cell membranes via glycosyl phosphatidylinositol (GPI) .
Prognostic Value
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Colorectal Cancer (CRC):
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Combined Biomarkers: A Tumor Marker Index (TMI) integrating CEA and CA19-9 improves CRC prognosis stratification (AUC = 0.739 vs. 0.682 for CEA alone) .
Therapeutic Applications
CEA’s overexpression in tumors has spurred targeted therapies:
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Cibisatamab: A CEA-CD3 bispecific antibody showing 50% radiological response rates in metastatic CRC when combined with PD-L1 inhibitors .
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Radionuclide Therapy: Anti-CEA antibodies (e.g., 90Y-DOTA-M5A) demonstrated stable disease in 56% of patients in Phase I trials .
Table 2: Clinical Trials Targeting CEA
| Therapy | Mechanism | Phase | Outcome | Source |
|---|---|---|---|---|
| Cibisatamab + Atezolizumab | Bispecific antibody + PD-L1 inhibitor | I | 50% response in CRC | |
| 90Y-DOTA-M5A | Radiolabeled anti-CEA antibody | I | Stable disease in 10/18 patients |
Diagnostic Innovations
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Multiplex Biomarkers: Combining CEA with CA19-9, CA72-4, and CA125 increases diagnostic sensitivity to 67.4% for CRC vs. 46.6% for CEA alone .
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Tissue Microarray Analysis: CEA expression patterns predict tumor aggressiveness; loss correlates with mismatch repair deficiency in CRC .
Limitations and Challenges
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False Positives: Benign conditions (e.g., cirrhosis, smoking) elevate serum CEA, reducing specificity .
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Heterogeneous Expression: Only 54.2% of 120 tumor types show consistent CEA positivity, limiting pan-cancer utility .
Future Directions
Emerging strategies include:
Product Specs
Q&A
What is Carcinoembryonic Antigen (CEA), and why is it significant in biomedical research?
Carcinoembryonic antigen (CEA) is a glycoprotein that belongs to the immunoglobulin superfamily. It is primarily expressed during fetal development in the gastrointestinal tract but becomes re-expressed in certain pathological conditions, including various adenocarcinomas such as colorectal, gastric, pancreatic, and non-small cell lung cancers . Its significance lies in its dual role as a tumor marker for diagnostic purposes and as a target for cancer immunotherapy .
The importance of CEA in research stems from its overexpression in malignancies, making it a valuable biomarker for monitoring disease progression, evaluating treatment efficacy, and developing targeted therapies. Additionally, its restricted expression in normal adult tissues minimizes off-target effects when used as a therapeutic target .
How is CEA detected in biological samples?
CEA detection typically involves immunoassays such as enzyme-linked immunosorbent assays (ELISAs), radioimmunoassays (RIAs), or chemiluminescent immunoassays. ELISA remains the most widely used method due to its sensitivity, specificity, and ease of use . The principle of ELISA involves capturing the antigen with a specific antibody immobilized on a microplate, followed by the addition of a secondary antibody conjugated to an enzyme. The reaction produces a measurable signal proportional to the antigen concentration.
For instance, Thermo Fisher's Human CEA ELISA kit employs a sandwich ELISA format with rigorous validation criteria to ensure reproducibility and reliability across different sample types such as serum, plasma, or cell culture medium . Table 1 below summarizes the key parameters of commonly used CEA detection methods.
| Method | Sensitivity | Specificity | Sample Type | Advantages | Limitations |
|---|---|---|---|---|---|
| ELISA | High | High | Serum, plasma | Easy to use; high throughput | Requires standardization |
| RIA | Moderate | High | Serum | High specificity | Radioactive materials required |
| Chemiluminescence | Very High | High | Serum, plasma | Extremely sensitive | Expensive equipment needed |
What are the primary clinical applications of CEA testing?
CEA testing is primarily used for monitoring cancer progression and recurrence rather than initial diagnosis. Elevated levels are associated with malignancies such as colorectal cancer but can also occur in other cancers like gastric or pancreatic adenocarcinomas . Clinicians often use serial measurements to track treatment response or detect early signs of recurrence after surgery or chemotherapy.
How do variations in assay methodologies impact the accuracy of CEA quantification?
Different assay methodologies can yield variable results due to differences in antigen extraction techniques, antibody specificity, and detection limits . For instance:
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Direct serum assays may show higher variability compared to plasma assays due to interference from other serum proteins.
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Double-antibody techniques enhance specificity by reducing cross-reactivity but require more complex protocols.
A comparative study demonstrated concordance rates ranging from 62% to 76% between different methods when using cut-off values of 5 ng/mL and 15 ng/mL for normal levels . This underscores the need for standardization across laboratories to ensure consistent clinical interpretation.
What are the challenges in developing CEA-targeted therapies?
Developing therapies targeting CEA faces several challenges:
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Immunogenicity: As a self-antigen, CEA elicits weak immune responses. Vaccination strategies using recombinant vaccinia viruses encoding human CEA have shown limited success in inducing high-avidity antibodies or cytotoxic T cells .
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Heterogeneity: Tumor expression of CEA varies among patients and cancer types, complicating universal therapeutic approaches.
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Off-target Effects: Although CEA expression is minimal in normal tissues, low-level expression can lead to unintended side effects.
To address these challenges, researchers are exploring prime-boost vaccination strategies and combination therapies that enhance immune activation while minimizing adverse effects .
How does smoking influence serum CEA levels?
Smoking induces epithelial cells to produce substances that cross-react with anti-CEA antibodies used in assays. This results in elevated baseline levels even in the absence of malignancy . Researchers must account for this confounding factor when designing studies involving smokers to avoid misinterpretation of data.
What role does CEA play in cancer metastasis?
CEA contributes to cancer metastasis by mediating cell adhesion and immune evasion. It interacts with cell surface molecules such as integrins and selectins to facilitate tumor cell attachment to endothelial cells during metastasis . Understanding these mechanisms provides insights into potential therapeutic targets for preventing metastatic spread.
How can researchers improve the sensitivity of CEA detection assays?
Enhancing assay sensitivity involves optimizing several parameters:
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Using high-affinity antibodies with minimal cross-reactivity.
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Incorporating signal amplification techniques such as chemiluminescence or fluorescence-based detection.
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Employing advanced sample preparation methods to reduce matrix effects caused by interfering substances.
Recent advancements include nanoparticle-based immunoassays that achieve femtomolar sensitivity levels while maintaining high specificity .
Product Science Overview
CEA was initially identified as a tumor marker for colorectal cancer. Its discovery marked a significant milestone in cancer research, as it provided a potential biomarker for the detection and monitoring of certain types of cancer . The protein is produced in large amounts by some tumors, making it useful for monitoring cancer treatment .
CEA belongs to a larger family of 12 carcinoembryonic antigen-related cell adhesion molecules (CEACAMs). These molecules have diverse functions in cell adhesion, intracellular and intercellular signaling, and during complex biological processes such as cancer progression, inflammation, angiogenesis, and metastasis . CEACAM1, CEACAM5, and CEACAM6 are now considered valid clinical biomarkers and promising therapeutic targets in various cancers, including melanoma, lung, colorectal, and pancreatic cancers .
Recombinant CEA is produced using recombinant DNA technology, which involves inserting the CEA gene into a suitable expression system, such as bacteria or mammalian cells, to produce the protein in large quantities. This recombinant form of CEA is used in various research and clinical applications, including the development of vaccines and immunotherapies .
CEA is widely used as a biomarker in clinical settings to monitor the progression and treatment of certain cancers. Elevated levels of CEA in the blood can indicate the presence of cancer or a recurrence of the disease after treatment. It is particularly useful in monitoring colorectal cancer, but it can also be elevated in other cancers, such as breast, lung, and pancreatic cancers .
Ongoing research aims to better understand the role of CEA and its related molecules in cancer and other diseases. The development of new molecular and biochemical tools, as well as mouse models, has enabled significant advancements in the study of the CEACAM network biology . These advancements may lead to new monitoring and targeting opportunities, improving the diagnosis and treatment of various cancers.
