CRO Chemistry: Antibody Drug Conjugates
Targeted Therapy for Cancer
Antibody-drug conjugates, or ADCs, are an important new class of biopharmaceutical drugs engineered to deliver potent anti-cancer agents directly to the target tumor. ADCs are composed of a tumor-specific antibody connected via a chemical linker to a biologically active drug or cytotoxic compound. By combining the exquisite targeting capabilities of an antibody with potent drug molecules, these innovative therapeutics are highly efficacious without the side effects of traditional chemotherapeutic agents.
Bioconjugation
NEDP offers bioconjugation services for Antibody Drug Conjugates (ADCs) utilizing the following general methodologies:
- Conventional cysteine conjugation: reduction of interchain disulfides followed by conjugation to electrophilic linker payloads (e.g., maleimide, haloacetyl)
- Site-specific cysteine conjugation: deprotection of mutant cysteine followed by conjugation to linker payloads
- Lysine conjugation: conjugation to lysine residues via activated ester-containing linker payload
ADC Process Research
Conjugation optimization employs a “design of experiments” (DOE)-based approach for rapid and efficient screening of all relevant reaction parameters such as linker-payload stoichiometry, concentration of solubilizing agents, reducing agents, oxidizing agents, pH of reaction medium, reaction temperature, agitation rate, addition rate, effect of co-solvents, etc. Using this approach, optimized processes are developed in a highly efficient manner.
Purification and Analytic Services
Purification is conducted use chromatography (HIC, IEX, mixed-mode, affinity) and/or ultrafiltration/diafiltration (UF/DF). ADC characterization including Drug Antibody Ratio (DAR), Unconjugated antibody (UmAb%), aggregation percentage, endotoxin level, and residual drug and related species levels are provided.
Design and Synthesis of Linker Payload
NEDP provides the linker payload services, including linker design, synthesis of linker payload, and related building blocks.