Novel Tools for Speedier Antibody-Drug Conjugate Discovery

Moradec offers unique secondary antibody-drug conjugates linked to MMAE, MMAF, DM1, or Duocarmycin, etc. Prescreening your target antibodies against cancer cells has become faster and cheaper with relevant mechanism of actions.

Antibody-drug conjugates (ADCs), which have become a new targeted therapy against cancer, consist of an antibody linked to a cytotoxic drug. The ADCs bind selectively to the target cancer cells via the monoclonal antibody portion. Internalization of the ADCs releases the drug to do its damage. This achieves target-specific killing of tumor cells while minizing systemic toxicity of the cytotoxic drug.

Secondary Antibody-Drug Conjugates

Prior to testing the function of ADCs in cell-based assays, each monoclonal antibody is typically conjugated directly with a cytotoxic drug. This step is time consuming and expensive, requiring milligram quantities of purified antibody, separate conjugation of each antibody, and further isolation of the ADC from the unconjugated drug. Using secondary antibody-drug conjugates (2°ADC) in a cell-based cytotoxic assay is a quick and economical alternative to pre-screening monoclonal antibodies as ADC candidates against tumor cells.

Instead of conjugating the monoclonal antibody with a cytotoxic drug, the naked monoclonal antibody is added directly to the cells in the presence of the 2°ADC. Internalization of the monoclonal antibody/2°ADC complex can achieve a similar effect of dose-dependent drug release within the cells as that of the monoclonal antibody-drug conjugate, while cells expressing low density of the targeted receptor are not affected.

Cell-based assays using Moradec's 2°ADC allow you to quickly screen an array of primary antibody leads and identify the best candidate for making specific ADC. In addition, Moradec offers a variety of 2°ADCs with cleavable or non-cleavable linker to different cytotoxic drugs, such as MMAE, MMAF, Dolastatin, Duocarmycin, and DM-1. Simultaneously testing the efficacy of multiple drug-linker combinations for your specific cell lines helps you to make better decision on the final format of your antibody-drug conjugate. Not only can the 2°ADC be used for screening antibodies, they can also be applied to recombinant protein ligands for targeting cell-surface receptors.

Moradec's 2°ADCs are highly specific with minimally toxicity to cells in the absence of primary antibodies. No obvious change of the primary antibody activity in the presence of the unconjugated secondary antibody.