The Chain: Protein Engineering Podcast

In a roundtable discussion, three experts bring perspectives on different methods for generating antibodies, including generating antibodies from naive libraries, patients, and immunizations. They discuss how the COVID-19 pandemic has highlighted the advantages of refocusing on infectious disease research. As well as the importance of having ready immune libraries and immunized mice, plus other approaches, ahead of any future infectious disease outbreak.  

The purification requirements in the biopharmaceutical industry will be even more demanding in the coming years due to increased awareness of product-related impurities like oligomers, variants, positional isomers, and glycoforms. These impurities need to be separated from the final product. Dr. Raja Ghosh’s work focuses on the design and development of efficient chromatography devices that combine high-speed with high-resolution in separation. He speaks with Dr. David Wood of the Ohio State University about how the chromatography devices he is developing address these challenges.  

On this episode of The Chain, Dr. Willem Overwijk shares his personal experience of his recent transition from academia to industry, and the differences between the two. Dr. Overwijk moved to industry, in part, to follow his research interest in a specific molecule that he had been working on since graduate studies: interleukin-2. Thanks to advances in protein engineering, this once ultra-potent molecule now can be administered with lower toxicity while still being an effective cancer therapy. We discuss IL-2, plus the exciting future of protein engineering in immuno-oncology. 

Dr. Dimiter Dimitrov, Director of the Center for Antibody Therapeutics at the University of Pittsburgh, sits down with The Chain to discuss his research and its relevance to the current pandemic. His work focuses on human VH domains, which in contrast to the animal antibody domains, like llama and shark, may have lower probability of immunogenicity. Dr. Dimitrov helps develop several such domains, most recently against SARS2, and one of which that is in production for evaluation in human clinical trials. Beyond COVID-19, Dr. Dimitrov explains that clinical trials for various cancer-related proteins and HIV are also underway, showing the vast potential for domains both for industry growth and life-saving therapies. 

Dan Chen returns for the Science Commune segment and speaks with Dr. Peter Marks, Director of the FDA’s Center for Biologics Evaluation and Research (CBER). Dr. Marks reflects on his fortuitous path from academia to industry to government, plus the differences between each area. Dr. Marks explains the research and regulatory role of CBER, especially as it pertains to the latest cell therapies. And finally, the two discuss the impressive speed of COVID-19 vaccine science breakthroughs and regulatory approval. 

Christian Klein is a longtime and key member of the protein and antibody community. In this episode, he speaks with Executive Conference Producer, Christina Lingham, on how the field has changed since their first collaboration. Dr. Klein offers an overview of the latest applications of bispecific antibodies, including the latest progress of clinical trials by Roche and others. He also explains how the PD1-X molecule is unique and can increase specificity of therapeutics even more. 

There are no bad ideas in developing bioanalytical testing, says Jim McNally, CSO of BioAgilytix. Not all ideas will work, of course. But he has found that it is the outside-the-box ideas that often turn out to be the solution in challenging assay work. Dr. McNally speaks with The Chain about his background in bioanalytical testing and supporting clinical trials, the exciting future of cell and gene therapies, and the importance of setting precedent in bioanalysis of these new, life-saving therapies. It is an exciting time for gene therapy especially, and Dr. McNally shares how new immunogenicity data is getting us closer to bringing this therapy to more people. 

There are some proteins that still evade scientists in the race for better therapeutics. Some of the most elusive drug targets in cancer research are RAS oncoproteins. In a paper published this July, researchers demonstrated the delivery of an extremely potent pan-RAS-cleaving enzyme, opening the door for the first targeted pan-RAS inhibitor for cancer therapy. In this episode we speak with two of the researchers from this project, a cancer biologist and a protein engineer, to learn what sparked their collaboration and what their system means for the future of cancer biologics. 

Carolyn Bertozzi grew up in a science family with a physicist father. But it was organic chemistry that “clicked” for Carolyn and started her down the path of understanding biology at a molecular level. Daniel Chen and Carolyn Bertozzi discuss her work in glycobiology. Bertozzi’s research finds that glycosylation has consequences in immune modulation, and that glycobiology plays an important role in human disease that has historically been underexploited in drug development. Finally, Chen and Bertozzi talk about gender representation in science and the importance of female role models for both women and men.

What was science like before the shift to big data technology? How did biologists learn about cells before we could do high throughput gene analysis? What we can learn about how to problem solve from those who helped get us to where we are today? In this Science Commune episode, Dr. Rik Derynck helps us answer those questions by sharing his stories as a young scientist in the “primitive” early days of cell biology. Derynck talks about his work on TGF-β and how his early pursuit of the unknown helped inspire new methodologies for problem solving that carry into his work today. Derynck looks towards the future of the field as biologists gain understanding of TGF-β’s role in cancer immunology and immunotherapy.