Development of Biparatopic CEA-targeted Bispecific ADCs

Antibody-drug conjugates (ADC) are emerging as powerful anticancer treatments and several ADCs have been approved for cancer treatment. ADC is designed to be stable in circulation and release potent cytotoxic drugs in tumor cells upon antigen-specific binding, uptake, and degradation. Efficient internalization and proteolysis in lysosome are essential for a successful ADC. However, for many cell surface proteins and carbohydrate structures on tumor cells, they are insufficient for an effective ADC internalization. Recently, the bispecific antibody (bsAb) approach has been found that can overcome this limitation and have been used in ADCs development.

Creative Biolabs is a leading developer and manufacturer focused on high-quality ADCs design and construction, and we can accelerate your program timelines, mitigate risks in the process, and fast tracke your program to completion. Our state-of-the-art mAb and ADC facility, and expert scientific team can optimize success from innovation through commercialization. Now we provide a full range of bispecific biparatopic ADCs development services targeting CEA antigen.

Introduction of CEA

Carcinoembryonic antigen (CEA) is a glycosyl phosphatidyl inositol (GPI) cell-surface-anchored glycoproteins involved in cell adhesion. The carcinoembryonic antigen family is composed of 29 genes, and 18 of which are normally expressed in humans. CEA serves as functional colon carcinoma L-selectin and E-selectin ligand, which may play a critical role in the metastatic dissemination of colon carcinoma cells. Immunologically, CEA is a member of the CD66 cluster of differentiation (including CD66a-CD66f). Normally, CEA is expressed by columnar and goblet cells in gastrointestinal tissue during fetal development, but the production stops before birth. Thus, CEA is usually present at very low levels in the blood of healthy adults. However, it is overexpressed on some types of cancer cells such as colonic cancer cells, which means that it can be used as a tumor marker in clinical tests. To date, CEA has been regarded as a vital prognostic marker for colorectal cancer diagnosis and therapy. Serum levels of CEA can also be elevated in heavy smokers.

Fig.1 Schematic representation of the human CEA gene and protein.

Biparatopic CEA-targeted Bispecific Antibody

Bispecific biparatopic antibody presents significant advantages compared with conventional monovalent antibody, including enhanced internalization and trafficking to the lysosomes by simultaneously targeting two different epitopes on the same antigen with a bispecific entity. Besides, it has been used in novel ADC development and showed enhanced internalization and trafficking to the lysosome by inducing clustering and cross-linking of receptors. Therefore, bispecific biparatopic antibody could be a new and effective component used in more potent ADCs construction.

A biparatopic antibody (BpAb) targeting CEA has been developed that has the capability of binding 2 different non-overlapping epitopes on the same target antigen molecule CEA. The biparatopic antibody demonstrated the advantage of biparatopic binding over conventional F(ab')2 binding. Besides, in vivo study results in nude mice xenografted with the human colon carcinoma T380 showed that the BpAb has higher tumor uptake than that of its parental F(ab')2. Thus, the biparatopic antibody (BpAb) may be used for ADC development to achieve a more effective internalization of ADC and more powerful tumor cell killing.

Fig.2 Mode of action of biparatopic ADC. (Chalouni, 2018)

What Can We Do for You?

Creative Biolabs is an acknowledged supplier in ADCs development services. We are committed to offering complete ADCs development and characterization services for more than ten years. Besides, we also provide various ADCs related products such as specific antibodies, potent drugs, and linker-payloads. We are confident that our services and products will promote your innovative bispecific biparatopic ADCs development against CEA protein. Please contact us for more information if you are interested in our services.

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