CEACAM5: A Promising Member of CEACAM Family, A Potential Target for ADC Drug Research!

1. What is CEACAM5?

CEACAM5 (carcinoembryonic antigen-related cell adhesion molecule-5), also known as CD66e or CEA, is a part of the CEA family (Click here to see "What is the CEA family?"). CEACAM5 is characterized by seven extracellular Ig chains and a glucosylphosphatidylinositol chain, exhibiting a domain structure of N-A1-B1-A2-B2-A3-B3 (Figure 1) ^[1]. Among the CEA gene family, CEACAM1, CEACAM5, CEACAM6, and CEACAM7 have crucial roles in tumorigenesis. While CEACAM1 and CEACAM7 are commonly down-regulated or absent in many tumors, indicating their function as tumor suppressor genes, CEACAM5 and CEACAM6 are often elevated in half of the tumors, acting as oncogenes ^[1-3].

CEACAM5 is widely found on the surfaces of different cell types, including endothelial, epithelial, and immune cells. It primarily functions as a cell adhesion molecule, promoting both homogeneous and heterogeneous adhesion in normal tissues. Similar to CEACAM6, it helps tumor cells evade apoptosis (Check the earlier CEACAM6 article here). Increased CEACAM5 and CEACAM6 levels can disturb cell polarity and hinder the maturation and differentiation of various cells, possibly contributing to tumorigenesis. Currently, CEACAM5 is used as a tumor marker for diagnosing various tumors and predicting their progression, deterioration, and subclinical metastasis ^{[1, 4-5]}.

Figure 1. Structure of CEACAM5 ^[5]

2. How's the CEACAM5-Related Signaling Mechanisms?

2.1 The Mechanisms of CEACAM5 in Tumors

CEACAM5 is highly expressed in most malignant tumors and is linked to tumorigenesis, invasion, and metastasis. Its mechanism of action, as part of CEACAMs, can be summarized in three key aspects: (i). Anti-adhesion - crucial for tumor invasion and metastasis, driving malignant tumor progression; (ii). Extracellular matrix (ECM) degradation - vital for tumor cell migration, with excessive CEACAM expression hindering apoptosis and disrupting cell structure; (iii). Activation of tumor signaling pathways-CEACAMs activate integrin signaling pathways, including elemental ILK and the PI3K. Notably, only GPI-anchored CEACAMs can bind to the α5β1 integrin receptor, exerting biological effects. Soluble CEACAMs lacking the GPI-anchor lose their binding ability, leading to apoptosis by blocking cell survival signaling from extracellular to intracellular processes (Figure 2) ^[6].

Figure 2. The mechanisms of CEACAM5 in tumors ^[6]

2.2 The Mechanisms of CEACAM5 in Platelet Activation

Platelets play a crucial role in tumor spreading and metastasis. CEACAM5/CEA, catabolized by PI-PLC/D, releases soluble sCEA, activating the c-Src kinase/MAP-ERK kinase pathway. This promotes cell adhesion, proliferation, migration, and microvascularization. Research shows that the extracellular segment of CEACAM5 inhibits certain platelet functions. Notably, MMP-12, MMP-2, MMP-7, and MMP-9 do not affect platelets through cleaving CEACAM5. This finding enhances our understanding of how CEACAM5 impacts platelets and tumor angiogenesis ^[7].

3. The Roles of CEACAM5 in Tumors Research

3.1 CEACAM5 and Colorectal Cancer Research

CEACAM5 is commonly used in early detection, diagnosis, and prognosis of colorectal cancer (CRC). Its elevated levels suggest potential disease progression. Studies connect increased CEACAM5 with higher recurrence risk in CRC patients. Combining the CDX2 test is suggested for comprehensive prognosis ^[9]. Additionally, positive SRCAP and CEACAM5 expression relate to higher postoperative recurrent metastasis rates, serving as predictors for recurrence after radical CRC surgery ^[10]. In conclusion, while crucial for early CRC management, CEACAM5 is often combined with other markers for accurate disease assessment.

3.2 CEACAM5 and Lung Cancer Research

Studies showed higher CEACAM5 expression in lung adenocarcinoma. Ualcan database analysis revealed significant differences between CEACAM5-positive and negative groups in various clinical factors. Kaplan-Meier survival analysis indicated lower survival rates in CEACAM5-positive patients. COX regression analysis identified CEACAM5, clinical stage, and lymph node metastasis as prognostic risk factors. Additionally, a positive correlation was found between CEACAM5, CEACAM6, and CEACAM1 in lung adenocarcinoma, suggesting their role in cancer development. These findings imply that high CEACAM5 expression is linked to poor prognosis in lung adenocarcinoma and may be a treatment target in lung cancer research ^[11].

3.3 CEACAM5 and Gastric Cancer Research

the MGd1 monoclonal antibody targets CEACAM5, allowing the assessment of its expression in gastric cancer patients for prognosis prediction. Analysis of 643 gastric tissues revealed increasing CEACAM5 expression from normal gastric mucosa to gastric cancer, emphasizing its role in cancer development. CEACAM5-positive non-cancerous gastric tissues were more prone to developing gastric cancer, suggesting its potential as a biomarker. Survival analysis of 143 gastric cancer patients indicated a positive link between CEACAM5 expression and deep cancer infiltration, particularly in advanced stages (IIIA-IV). Thus, CEACAM5 serves as an independent prognostic indicator for gastric cancer, correlating with poorer survival ^[12].

3.4 CEACAM5 and Breast Cancer Research

RT-qPCR analysis examined KRT19 mRNA and CEACAM5 mRNA-labeled CTC levels in preoperative peripheral blood of breast cancer patients. Results showed higher CTC KRT19-positive and CTC CEACAM5-positive expression rates in metastatic breast cancer patients (stage IV) compared to earlier stages (0-III). These findings support KRT19 and CEACAM5 as potential biomarkers for predicting breast cancer metastasis. In breast cancer, markers like KRT19 and CEACAM5 in serum or tumor tissue have been used to detect metastasis and predict prognosis ^[13].

3.5 CEACAM5 and Other Tumors Research

Research on CEACAM5 in various cancers has increased in recent years. In Mucoepidermoid Carcinoma (MEC) of the salivary glands, high CEACAM5 and PCNA expression indicates increased malignancy, aggressiveness, lymph node metastasis, and poor prognosis. Evaluating CEACAM5 and PCNA levels in salivary gland tumor patients can help determine malignancy and prognosis, guiding treatment decisions ^[14]. Additionally, CEACAM5 is overexpressed in pancreatic, gallbladder, female reproductive system, medullary thyroid carcinoma, bladder, and prostate tumors, highlighting its potential as a versatile tumor marker and immunotherapy target ^[15-20]!

4. The Clinical Research of CEACAM5 Targeted Therapy

Currently, there are 15 drugs related to CEACAM 5 in development, including monoclonal antibodies, bispecific antibodies, CAR T cell therapies, trispecific antibodies, diagnostic radiopharmaceuticals, and therapeutic vaccines. Sanofi's Tusamitamab ravtansine, in phase III trials for non-small cell lung cancer, is the most advanced. Other drugs are in various clinical phases, such as the bispecific antibodies: Labetuzumab govitecan (CEACAM 5 x TOP1), BGB-B167 (CEACAM 5 x 4-1BB), M-9140 (CEACAM 5 x TOP1), CT-109 (CEACAM 5 x CEACAM6), YB-200 (CEACAM1 x CEACAM 5), CEACAM5 x CD3; triple-specific antibodies: PM-4008 (CEACAM 5 x CD3 x CEACAM6); CAR T: Anti- CEA CAR T cell therapy; Vaccine: Cancer vaccine (CEACAM 5 x MUC1); diagnostic radiopharmaceuticals: TF 2-targeted cancer therapy, etc. These developments suggest a promising future for CEACAM5 as a tumor target.

In Conclusion:

CEACAM5, a cell adhesion molecule and member of the CEA family, is overexpressed in various cancers, notably colorectal, lung, gastric, and breast cancers. Its high expression often correlates with aggressive tumor behavior and poor prognosis. Studies suggest its utility as a diagnostic marker for cancer detection and prognostic evaluation. Ongoing drug development targeting CEACAM5 includes monoclonal antibodies, CAR T cell therapies, and bispecific antibodies, indicating its potential as a valuable therapeutic target in cancer research.

5. CUSABIO CEACAM5 Recombinant Proteins & Antibodies for Research Use

To fully support researchers and pharmaceutical companies in their research on CEACAM5 in tumors, CUSABIO presents CEACAM5 active proteins & antibodies to support your research on the mechanism of CEACAM5 or its potential clinical value.

CUSABIO CEACAM5 Protein

Recombinant Human Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) (E398K) (Active) Code: CSB-MP005165HU

High Purity Validated by SDS-PAGE

The high purity is greater than 95% as determined by SDS-PAGE.

Excellent Bioactivity Validated by Functional ELISA

Immobilized Human CEACAM5 at 2μg/mL can bind Anti-CEACAM5 recombinant antibody (CSB-RA005165MA1HU). The EC₅₀ is 0.8955-1.719 ng/mL.