BOC Sciences provides the most complete set of solutions in antibody-drug conjugate (ADC) drug development services in the pharmaceutical industry. Working with companies and academic groups all over the world, including most of the top biopharmaceutical companies, our ADC technology supports the development and manufacture of antibody-drug conjugates. We are equipped with cGMP grade laboratory facilities and system, and our personnel is well versed in linker and cytotoxin conjugations technologies. We have a dedicated custom development platform that it's very convenient for customers to customize different ADC products and services.
Calicheamicins are members of the enediyne class of antitumour antibiotics, originally isolated from fermentations of Micromonospora echinospora ssp. calichensis, among which the iodine-containing calicheamicin γ1I is the most potent. Targeted delivery of immunoconjugates of ozogamicin with antibodies specific for tumour-associated antigens, e.g., gemtuzumab for CD33 and inotuzumab for CD22, are clinically used (Mylotarg® and Besponsa®, respectively) in the treatment of several hematologic malignancies. Interest in this type of drugs is very much alive nowadays because several enediynes provide useful payloads for next-generation antibody-drug conjugates with greater homogeneity, less tendency to aggregate, higher tolerability and enhanced in vivo stability.
Fig. 1. Structural and mechanistic insight into DNA bending by antitumour calicheamicins (Org. Biomol. Chem. 2021, 19: 6707-6717).
Linkers Screening and Design For Calicheamicin Cytotoxins
In addition to hydrazone linkers already applied to calicheamicins toxins, BOC Sciences also provides screening and custom development services for other universal linkers for calicheamicins toxins, such as disulfide linkers , amide linker, thioether linker and enzymatically cleavable linkers . We are committed to facilitating the development of next-generation ADC linkers with enhanced plasma stability. Our scientists tune-up key linker parameters such as coupling chemical site, linker length, and linker steric hindrance for specific payloads to achieve a balance between ADC stability and payload release efficiency.
Targets Screening For Calicheamicin-Linker Conjugates
As a highly specialized ADC service provider, we can screen semi-finished calicheamicin-linker conjugates for therapeutic targets or customize calicheamicin-linker conjugates based on our customer research target needs to increase treatment opportunities for solid tumors and other cancer diseases. Our advanced organic synthesis platform facilitates the design and preparation of various drug-linker complexes for ADCs development. Our ADC target development customized services include:
Antibodies Screening and Modification For Calicheamicin-Linker Conjugates
The steric shielding of antibodies can be obtained by selecting coupling or attachment site with greater steric hindrance. Furthermore, alternative chemical modifications introduced by steric hindrance at the linker proximal end have been proved to be an effective approach to improve the stability of ADC drugs. The steric shielding provided by antibody helps reduce linker cleavage as well as payload metabolism. With years of experience in antibody development, BOC Sciences will screen and design the most suitable antibody based on the type, length and steric hindrance of the payload and linker conjugates.