Discovery and Manufacturing Strategies for Novel, Homogeneous ADC Molecules

Video   Dec 23, 2016

 

Several key learnings have emerged through application of rapid re-iterative ADC design using reactive non-natural amino acids to specifically position conjugation sites: Site-specific homogeneous molecules can improve therapeutic index preclinically and have the potential to optimize clinical impact for a given combination of antibody and warhead. Site matters. Homogeneity is required, but not sufficient, for best in class molecules. Finding the optimal site for conjugation is crucial. Beyond antibody stability, PK and attributes that optimize for internalization and cell killing in vitro, certain conjugation sites on the antibody further enhance solid tumor killing efficacy in vivo. The antibody production process has been split into two stages; First the production of the ribosome-rich extract that can now be considered a critical raw material. And secondly, use of that cell-free extract to produce nnAA containing antibodies in 10 hours from DNA. Each stage has been optimized for speed, efficiency and flexibility and now established as a viable manufacturing process: Removal of RF-1 from the extract permits very efficient production of nnAA containing Use of novel nnAAs allows complete conjugation in minutes Extracts that incorporate orthogonal tRNAs and lack RF-1 provide for efficient and flexible manufacturing.

 
 
 
 

Recommended Videos

How to Grow Flu Inside an Egg

Video

Infectious disease researcher Matthew Miller shows how his lab grows the flu inside an egg. Work in Miller's lab could one day lead to a universal flu vaccine.

WATCH NOW

Immunology Wars: The Role of Monoclonal Antibodies

Video

Our immune systems are at war with cancer. This animation reveals how monoclonal antibodies can act as valuable reinforcements to shore up our defences – and help battle cancer.

WATCH NOW

Biggest Science News Stories of 2017

Video

We have seen some amazing scientific breakthroughs in 2017, here is a selection of our favourites.

WATCH NOW

 

Comments | 0 ADD COMMENT

Like what you just watched? You can find similar content on the communities below.

Biopharma Immunology & Microbiology

To personalize the content you see on Technology Networks homepage, Log In or Subscribe for Free

LOGIN SUBSCRIBE FOR FREE