BOC Sciences possesses GMP-grade contract manufacturing facilities and exploits a custom development platform of antibody-drug conjugates. We can guarantee researchers high-quality products from gram to kilogram scales and professional technical support to help our clients win the race of ADC research. As a highly specialized ADC service provider, we focus on providing our clients with customized linker-cytotoxin conjugate products. In addition, we can provide all the raw materials required for ADC development.
Monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) are effective anti-cancer microtubule-targeting agents (MTAs) used as payloads in many approved MMAE/MMAF-containing antibody drug conjugates (ADCs) and multiple ADCs in clinical development to treat different types of cancers. For example, brentuximab vedotin (Adcetris®), an ADC drug targeting CD30 of cancer cells, was approved by FDA in 2011 for the treatment of anaplastic large cell lymphoma (ALCL). Mechanistically, the antibody of Adcetris® is linked to the payload MMAE via a protease-cleavable linker Val-Cit, which is coupled to cysteine (cys) residues. Then, Adcetris® is internalized by attachment to CD30 and then transported to the lysosome. Finally, MMAE is released through the proteases cleavage in lysosomes, exerting cytotoxic effects and inducing apoptosis. Currently, MMAE and MMAF is the most widely applied warhead in the development of ADCs.
Fig. 1. Structural of Trodelvy® (MAbs. 2021, 13(1): 1951427).
In addition to the MMAF/MMAF-linker conjugates already used for ADC drugs, such as Val-Cit-MMAE, MC-Val-Cit-MMAE, MC-Val-Cit-PABC-MMAE, and MC-MMAF, BOC Sciences also provides development and manufacturing services for linkers based on MMAE/MMAF payloads. With advanced instruments and experienced R&D teams, we provide linker and cytotoxin conjugation services for our clients with cost-effective to shorten the development cycle of new ADC drugs. Furthermore, BOC Sciences' supply and synthesis process technology can provide various ADC products and development services for your research and production needs.
The successful development of ADC depends on the specific binding between antibodies and target antigens. The ideal ADC targets are highly expressed on the tumor cell surface and low or not expressed in normal tissues. Targets expressed in normal tissues will be taken up by ADC drugs, leading toxic off-target effects and reducing the therapeutic window of ADC drugs. In addition to providing target screening services for linker and cytotoxin conjugation intermediates, BOC Sciences also provides one-stop synthesis services and target screening solutions for linkers, cytotoxins, and linker-cytotoxin conjugates. We have a dedicated custom development platform that is very convenient for our customers to customize different ADC products and services. Our ADC target development customized services include:
Currently, antibodies applied to ADC drugs are mainly IgG molecules, which have high affinity for target antigen and long half-life in blood. With years of experience in antibody modification, BOC Sciences’ IgG antibody modification capabilities cover IgG1, IgG2, IgG3, and IgG4, especially suitable for ADC drug screening of IgG1 scaffold. As you know, our ADC antibodies are chimeric humanized antibodies or fully humanized antibodies. Additionally, we also offer overall ADC product development and supervision support through the development of manufacturing processes and quality control methods.