ADC Development Services Targeting CD138

CD138 is a promising target for the treatment of multiple myeloma (MM) and being studied as an important target for antibody-drug conjugate (ADC). Scientists at Creative Biolabs are focusing on applying excellent science and technology to discover and develop potential new ADCs with the goal of becoming first-in-class therapeutics. We provide custom ADCs design, construction and charaterization services. Creative Biolabs also provides our worldwide customers customized anti-CD138 ADC development services according to your specific demands. Besides, the off-the-shelf Anti-CD138 ADC Products are available for you.

Introduction of CD138

CD138, also known as syndecan-1, is the most characterized member of the syndecan family, which constitutes a major class of cell surface heparan sulfate proteoglycans (HSPGs). The large extracellular domain of CD138 binds via its heparin sulfate chains to soluble extracellular molecules, including the epidermal growth factor, hepatocyte growth factor, fibroblast growth factor, and to insoluble extracellular molecules, such as fibronectin and collagen. CD138 is involved in several cellular functions, such as cell-cell adhesion, migration, signaling, cell-matrix interactions and proliferation. Within the normal human hematopoetic compartment, CD138 is expressed on differentiated plasma cells and is a primary diagnostic marker for MM. Its expression has also been found in breast and other carcinomas, possibly indicating other potential applications of CD138-targeted therapies.

Schematic illustration of syndecan-1 to syndecan-4. Fig.1 Schematic illustration of syndecan-1 to syndecan-4. (Szatmári, 2013)

Anti-CD138 ADC in Multiple Myeloma

CD138 is a highly attractive target for cancer therapy. Indatuximab ravtansine (BT062), an anti-CD138 ADC, was able to demonstrate anti-tumor efficacies for MM in preclinical experiments. BT062 is an ADC consisting of the anti-CD138 chimerized monoclonal antibody (mAB) nBT062 and the microtubule-binding cytotoxic agent maytansinoid DM4. nBT062 is a hinge-unmodified human IgG4 chimerized antibody based on the murine B-B4 precursor. BT062 specifically targets CD138-expressing cells, once internalized, lysosomal processing of its linker results in the release of DM4, which in turn binds to tubulin and causes cell cycle arrest followed by apoptotic cell death. BT062 is currently evaluated in several clinical trials.

Illustration of a malignant plasma cell showing the mechanism of action for ADCs. Fig.2 Illustration of a malignant plasma cell showing the mechanism of action for ADCs. (Sherbenou, 2015)

What Can We Do for You?

Efforts to broaden the applicability of antibodies to MM by targeting antigens more specific to the disease are finally coming to fruition. Since mAbs could be specifically developed to target signaling pathways responsible for myeloma cell survival, proliferation and microenvironment interaction, efficacy can be further accentuated by linkage of these developed mAbs to cytotoxic small molecules. Creative Biolabs is fully capable of generating different engineered antibodies targeting CD138. These antibodies could be further conjugated with different kind of toxins via various linker to form innovative ADC through our advanced technique platform. Creative Biolabs offers a whole suite of technique platform/services needed for the anti-CD138 ADC development including but not limited to the following:

Schematic half antibody exchange and respective nBT062 model antibodies. Fig.3. Schematic half antibody exchange and respective nBT062 model antibodies. (Herbener, 2018)

Experienced in antibody engineering and linker-payload synthesis, Creative Biolabs has perfected our technical pipelines in the development of high-quality ADC products. If you are interested in our anti-CD138 ADC development services for MM, please feel free to contact us for more information.

References

  1. Szatmári, T.; Dobra, K. The role of syndecan-1 in cellular signaling and its effects on heparan sulfate biosynthesis in mesenchymal tumors. Frontiers in Oncology. 2013, 3: 310.
  2. Sherbenou, D. W.; et al. The development of potential antibody-based therapies for myeloma. Blood reviews. 2015, 29(2): 81-91.
  3. Herbener, P.; et al. Functional relevance of in vivo half antibody exchange of an IgG4 therapeutic antibody-drug conjugate. PloS one. 2018, 13(4): e0195823.

For Research Use Only. NOT FOR CLINICAL USE.


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