BOC Sciences has established an end-to-end integrated service platform for ADC products, ranging from the development and production of biologics, small molecules, and conjugation technologies to comprehensive analytical characterization services for ADC products. Our ADC development platform is equipped with advanced ADC synthesis, separation and purification and testing equipment to ensure a stable commercial production process and are an ideal business partner for your GMP ADC needs. We can complete contract manufacturing at low cost on the premise of ensuring quality, saving your project expenses.
Pyrrolobenzodiazepines (PBDs) are sequence selective DNA minor groove binding ligands, which have received considerable attention because of their potent antitumour activity, which results from covalent binding of the C11 position of the diazepine ring to the 2-amino group of a guanine. Naturally occurring PBDs include anthramycin, tomaymycin, neothramycin and sibiromycin. Synthetic PBD monomers with C2 (pyrrolidine ring)-aryl substitution exhibit nanomolar to picomolar cytotoxic potency against a number of tumour cell lines. For example, Lonca®, a CD19-targeting ADC therapy, consists of humanized anti-human CD19 monoclonal antibodies coupled with PBD dimer cytotoxins via enzymatically cleavable valine-alanine linkers. Mechanistically, Lonca® will be internalized after binding to the CD19-expressing cells. Then, cytotoxins are released and bind to DNA irreversibly, creating strong interchain crosslinks to prevent DNA chain separation, thus disrupting essential DNA metabolic processes such as replication, and ultimately leading to cell death.
Fig. 1. PBD-ADC manufacturing process and the PBD structure (Journal of Pharmaceutical and Biomedical Analysis. 2020, 179: 113027).
Linkers Screening and Design For PBD Cytotoxins
In addition to enzymatically cleavable linkers already applied to PBD cytotoxins, BOC Sciences also provides linker custom development and integrated design services for PBD cytotoxins such as disulfide linkers, amide linkers, thioether linkers, acid cleavable linkers/hydrazone linkers ect. Our experienced scientists specialize in tuning key linker parameters for specific payloads, such as linker length, linker steric hindrance, and the selection and modification of coupling chemical sites to tune ADC payload release for optimal efficacy.
Targets Screening For PBD-Linker Conjugates
Currently, ADC drugs are mainly used in the tumor fields. Thus, antigen targets are required to be highly expressed in tumor cells, but low or not expressed in normal tissues, or only expressed in specific tissues. Secondly, target antigen should exist on the cell surface so that the circulating mAb can enter. Simultaneously, the antigen target should have endocytic capacity to trigger the transport of ADC-antigen complexes into cells. With a good record in the development of ADC projects, BOC Sciences' experienced scientists enable to help our clients quickly complete the challenging target screening processes. Our disease research services including:
Antibodies Screening and Modification For PBD-Linker Conjugates
In terms of antibody types, the ADC drugs currently under development use immunoglobulin G (IgG). Studies have shown that IgG has high affinity for target antigen and long half-life in the blood circulation, making it ideal for the antibody portion of ADCs. BOC Sciences' antibody modification-conjugation platform enables screening services against the natural binding sites of different antibody subtypes. Furthermore, we can modify antibodies to create new active sites to enhance ADC stability or antibody specificity. Our antibody modification-conjugation services include IgG1, IgG2, IgG3 and IgG4 subtypes. Moreover, we also developed the ADC analysis process line and will continue to adjust it as the process changes.
BOC Sciences' high-potency cytotoxins act on various immune checkpoints with well-defined mechanisms, including microtubule, DNA, and DNA topoisomerase. Our cGMP manufacturing capabilities enable synthesis scale for payloads ranging from milligrams to grams.