This week we interviewed Jacob Glanville, a computational immunoengineer who co-founded Distributed Bio, a company focused on applying computationally-guided immunoengineering methods to enable a new generation of monoclonal antibody discovery and universal vaccine design. He applies his hybrid expertise in computational biology, immunology and bioengineering towards the next-generation sequence analysis and interpretation of antibody repertoires and rationally designed libraries.
As a PhD graduate in the nascent Computational and Systems Immunology program at Stanford University, he worked with Scott Boyd, Mark Davis and many other collaborators on fundamental questions of systems biology of human immune components, and acted as instructor for multiple applied computational immunology courses.
Jacob will be speaking in the Protein is the Killer App session (Sponsored by Codexis) at SynBioBeta SF 2017 on October 4th. He will be presenting a workshop earlier on the same day on how to generate high affinity antibodies within seven days, so if you are interested in learning about his methodology, make sure to register for the event!
Why is immunoengineering such an exciting field to be part of at the moment?
We are in a golden age for both immunology and bioengineering. In immunology, it has become increasingly recognized that almost every pathological state has an immunological component, including not only traditional areas such as infection, autoimmunity, allergy, transplant and vaccine science, but also increasingly into oncology, heart disease, neurodegeneration, and a myriad of other pathologies.
This is because fundamentally our immune systems are a pattern recognition system designed to detect and respond to changes in our healthy tissues compared with an infinity of foreign or abnormal states. This appreciation has coincided with radical new advances in high-throughput immune interrogation as well as high throughput synthetic control of the immune response: a revolution in immunoengineering for human health and longevity.
Can you tell us a little about your projects at Distributed Bio, and about antibody library analysis and design?
For the last 462 million years, over 60,000 jawed vertebrate species have chosen antibodies as their preferred molecule of adaptive protection. In the last twenty-five years monoclonal antibodies as therapeutics have been adopted by the pharmaceutical industry, rapidly surpassing traditional small molecule discovery in both discovery and portfolios.
Distributed Bio leverages computational immunology to mathematically optimize synthetic immune systems to enable antibody discovery, and optimize antibody engineering of discovered antibodies to imbue them with new pharmacologically desirable characteristics. Our technologies are licensed to over 40 partners and are used internally to develop a new wave of optimized monoclonal medicines.
AbGenesis is a computational immunology platform for mining of antibodies, TCRs and peptides, used at over 30 institutions and biotechnology companies, including 6 of the 10 top pharma.
What challenges persist in your field, and what progress has your team – or other peers – made in overcoming them?
Antibodies are great therapeutic scaffolds, but are challenging to engineer. Containing over 40 chiral centers in the traditional “paratope” target binding site, they are orders of magnitude more complex than small molecule drugs like aspirin or viagra. Using high-throughput sequencing, carefully designed algorithms, and appropriate experimental selection pressures, we are able to enumerate the “fitness function” of antibodies at high-throughput.
This approach provides a route forward for rational engineering of biomedicine that side-steps the fundamental limitations of structural energetics prediction. For a patient, this means a new generation of drugs that can be received as a shot rather than an IV infusion, can be administered every two months rather than two weeks, will have less toxic side effects, and will be more likely to provide therapeutic effect: a second wave in rational engineering of biomedicine.
What are the upcoming milestones and long-term priorities for your company?
Distributed Bio has built a widely adopted computational analysis platform (AbGenesis) and a computationally optimized discovery platform (the SuperHuman library). By the end of 2017 we will have announced multiple partnerships on specific IO molecules emerging from our library, and by 2018 we will have achieved POC for internally developed Distributed Bio therapeutic programs. In addition to engineering antibodies, our engineering of antigen repertoires represents a powerful new epitope focusing technology with universal vaccine applications.
What are you most looking forward to at SynBioBeta SF 2017?