Tumor-Associated Le^b Antigen Production Service at CD BioGlyco

• The role of Le^b antigen in cancer study

In the human colon, Le^b antigen expression evolves through development and cancer progression. While Le^b antigens are prevalent in the fetal colon, their presence diminishes in the distal colon postnatally, with limited expression in the proximal colon in adulthood. In contrast, Le^a antigens maintain a consistent distribution post-birth. Colorectal carcinoma advances through stages, including hyperproliferation, dysplasia, adenoma formation, carcinoma development, and metastasis. Immunohistochemical studies reveal Le^b and Le^y antigen resurgence during adenoma stages, intensifying as tumors progress, notably in distal colon cancer. This Le^b antigen resurgence is a valuable marker for distinguishing malignancy, aiding early diagnosis and differentiation from non-malignant conditions.

Fig.1 (A) Le^b is within hydrogen bonding distance (3.3 Å) of Tyr62 from the LLYlecwt domain. (B) A Y62H mutation was designed to retain similar structural properties to tyrosine, with the possibility that it may also result in a hydrogen bond to the Le^y antigen. (Lawrence, et al., 2012)

• The synthesis of Le^b antigen

According to different glycosidic bonds, Lewis antigens are classified as type I and type II. We have developed the Glyco™ Vaccine Development Service Platform to provide high-quality Tumor-Associated Carbohydrate Vaccine Development services to our clients around the world, specifically the Tumor-Associated Lacto-series Antigen Production Service. It is a common production strategy to regulate the production of Le^b antigen products by regulating the gene expression of the relevant enzymes according to the Le^b biosynthetic pathway. Here are the pathways on which our services are based.

The H type I structure is generated by adding fucose (Fuc) to the type I structure through the action of α1,2fucosyltransferases (α1,2Fuc-Ts). Subsequently, the Le enzyme adds Fuc to the H type I structure to create Le^b antigens. Our previous research has shown that Le^b expression on erythrocytes, as well as secretor status determination, is exclusively governed by the Se enzyme. On the other hand, the H enzyme is solely responsible for determining ABH antigen expression in erythrocytes. In colon tissues, both α1,2Fuc-Ts, namely the Se and H enzymes, are expected to participate in the synthesis of H-type I structures, eventually leading to the production of Le^b antigens.

Fig.2 Lewis antigens biosynthetic pathways. (Ma, et al., 2021)

• The standard process of Le^b antigen production used in vaccine development

Here is the standard process of our service, the Le^b antigens are formulated into a vaccine. Depending on the type of vaccine, they may be combined with adjuvants, carriers, or other immune-stimulating molecules to enhance their immunogenicity. Le^b antigen-based vaccines hold promise in cancer immunotherapy, offering a targeted approach to combat specific cancers that overexpress these antigens. They are part of ongoing efforts to harness the immune system's capabilities to fight cancer and improve patient outcomes. We look forward to your contacting us to inquire about the details!

Fig.3 A series of enzymatic reactions that result in the synthesis of Le^b antigens. (CD BioGlyco)

Applications of Tumor-Associated Le^b Antigen Production Service

• Le^b antigen can serve as a valuable biomarker for the detection and diagnosis of gastrointestinal cancers, particularly in cases where other markers like CA19.9 are not effective.
• Researchers can employ Le^b antigen in studies related to cancer biology, glycosylation patterns, and genetic factors influencing antigen expression.

Advantages of Us

• Our talented scientists and well-experienced laboratory team can perform our experiments and subsequent data analysis in good quality.
• We provide one-stop tumor-associated Le^b antigen production services for clients, from extraction and purification to characteristics and quality control.
• Our service team consistently provides exceptional customer support, offering prompt and helpful assistance to address client needs and inquiries.

CD BioGlyco is a company with extensive glycan chemistry research experience and aims to be clients’ best glycan research cooperator. Please do not hesitate to contact us if you are interested in our services and would like to have a further discussion with us.

References

1. Lawrence, S.L.; et al. Manipulating the Lewis antigen specificity of the cholesterol-dependent cytolysin lectinolysin. Frontiers in Immunology. 2012, 3: 330.
2. Ma, Z.; et al. Expression of the carbohydrate Lewis antigen, sialyl Lewis a, sialyl Lewis X, Lewis X, and Lewis y in the placental villi of patients with unexplained miscarriages. Frontiers in Immunology. 2021, 12: 679424.
3. Indellicato, R.; et al. Complementary use of carbohydrate antigens Lewis a, Lewis b, and Sialyl-Lewis a (CA19. 9 Epitope) in gastrointestinal cancers: biological rationale towards a personalized clinical application. Cancers. 2020, 12(6): 1509.