ADC Development Services Targeting Integrin αV

As a pioneer in the field of bio-conjugation for over ten years, Creative Biolabs has successfully completed a significant number of antibody-drug conjugates (ADCs) development projects. Our customers, ranging from small biotech to large pharmaceutical companies, have taken full advantage of our ADCs and bioconjugation capabilities. Our state-of-the-art facility, staffed with a dedicated team of experts, has been in operation for several years and can support you in delivering the promising ADC candidates targeting the integrin αV.

Introduction of Integrin αV

Integrins are a type of transmembrane receptors that can interact with the extracellular matrix proteins or other adhesion receptors on neighboring cells. Integrin αV is a member of the integrins family encoded by the ITGAV gene. It contains an alpha chain and a beta chain and possesses the ability to combine with multiple substrates including β1, β3, β5, β6, and β8. In addition to adhesion, Integrin αV is involved in regulating signal transduction. Besides, the interaction of integrins and ligands functions in the regulation of the sprouting ability of endothelial cells during angiogenesis, localization of inflammatory cells recruited to sites of repair, or the invasive potential of tumor cells. What’s more, integrin αV plays an important role in the tissue remodeling, tumor-associated angiogenesis and the growth and progression of tumors. Therefore, Integrin αV has been considered as a potential target in the treatment of cancer.

A model for αv integrin-mediated adhesion and signaling events during metastatic tumor cell growth and survival in the liver. Fig.1 A model for αv integrin-mediated adhesion and signaling events during metastatic tumor cell growth and survival in the liver. (McCarty, 2008)

Anti-integrin αV ADC in Solid Tumors

Integrin αV as a useful biomarker has been used in the targeted ADCs immunotherapy for the solid tumors. For example, immunoconjugate IMGN388 is an ADC has been designed to target the integrin αV. It is composed of an anti-integrin αV antibody covalently conjugated to the cytotoxic agent maytansinoid DM4 through a cleavable disulfide linker.

Upon the IMGN388 binds to tumor cell surface integrins, following internalization, the DM4 payload can be released and bind to tubulin and disrupt microtubule assembly/disassembly dynamics, resulting in the inhibition of cell division and cell growth of integrin-expressing tumor cells. Preclinical trial results demonstrated that the ADC has potent antitumor activity against a variety of solid tumors, such as human xenograft lung, colon, pancreatic, ovarian and breast tumors in nude rat models. Besides, IMGN388 showed well toleration and safety in early clinical phase I study. All results indicated that this ADC is a promising therapeutic agent for solid tumors therapy.

Structure of IMGN388. Fig.2 Structure of IMGN388. (Lu, 2016)

What Can We Do for You?

Creative Biolabs has more than 10 years of experience in antibody discovery and production, drug synthesis and bio-conjugation. Our highly qualified, experienced & motivated staff members, along with their extensive project management experience, provide integrated ADCs design and development services. At present, we offer a comprehensive set of ADCs construction services against specific tumor-associated antigens such as the integrin αV. Below you will find just some of the services our team provides:

If you want to know more information, please feel free to contact us.

References

  1. McCarty, J. H. αv Integrins lead the way for colorectal metastases. Clinical Cancer Research. 2008, 14(20): 6351-6353.
  2. Lu, J.; et al. Linkers having a crucial role in antibody-drug conjugates. International journal of molecular sciences. 2016, 17(4): 561.

For lab research use only, not for any in vivo human use.


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