Challenges and limitations of ADC development

One of the major challenges of modern medicine is to find a safe cancer therapy. The Food and Drug Administration has approved Adcetris® (brentuximab vedotin) and Kadcyla® (ado-trastuzumab emtansine) that are considered as powerful treatments against cancer. They are good examples of antibody-drug conjugates (ADCs). The principle is to link a drug, that can be cytotoxic, to an antibody able to target cancer cells. Unfortunately, the development of ADCs faces some difficulties. Indeed, depending on the method for the conjugation, the ADC can be highly heterogenous.

This summer, Moffett et al. published in Nature Communications (Nature Communications – doi:10.1038/s41467-017-00505-8) a new approach for cancer therapeutic research and development based on mRNA delivery. They called it ‘Hit-and-run programming’ because of the simplicity of the method. Interestingly, the optimization of the delivery was performed with eGFP mRNA.  This post describes how TriLink’s mRNAs contribute to the simple and efficient delivery of mRNA into cells.

Expression systems – removing their contaminants

CHO, E. Coli and Pichia are useful expression systems for drug production. This can be for proteins, enzymes or antibody productions. Research and development for therapeutic perspectives requires a high level of quality controls. Such expression systems contain +1000 host cell proteins (HCPs). A major challenge in biological component production is to remove this HCP contamination. In order to monitor removal efficiency (during protein purification, as mentioned further on in this article), Canopy Biosciences have developed and optimised HCP detection kits based on the principle of the sandwich ELISA test as illustrated below.

Principle of the HCP Detection assay is based on sandwich ELISA test – by Canopy Biosciences at tebu-bio.com

HepatoSure® is a pool of human hepatocytes designed to facilitate your DMPK applications with a consistent hepatocyte product over time (years). HepatoSure® is best suited for both discovery and development of ADME-Tox study assays where generation and comparison of data is required. Let’s take a closer look, and you might like to benefit from our current offer to try these for yourself (see below).