The complete remission from advanced rectal cancer observed in all patients who took part in a small clinical trial echoed strongly in global news channels earlier in 2022 (Cercek et al., 2022). “I believe this is the first time this has happened in the history of cancer” is how the NEJM study lead Dr L Diaz, an oncologist at Memorial Sloan Kettering Cancer Center, framed the study’s success to the New York Times. The drug used in this study, the monoclonal antibody dostarlimab, a check point inhibitor to programmed death receptor-1 (PD-1) is part of a growing class of medicines that significantly improve the quality of healthcare, biologics.
Biologics discovery and benefits of phage display
The NEJM study comes some twenty years after the discovery and commercialization of the most successful biologic by sales, Humira, a number only recently surpassed by Covid-19 vaccines during the pandemic. Humira (adalimumab) achieved revenues of ~$18 billion in 2017 and is now a key medicine that enables physicians to fight rheumatoid arthritis as well as other debilitating autoimmune and inflammatory diseases. The technology that identified Humira, phage display, is common practice in laboratories today, but has evolved significantly since its inception by Nobel Prize winners George P. Smith and Sir Gregory P. Winter. From antibody libraries focused mainly on identifying high affinity antibodies, today’s libraries need also to deliver additional properties including specificity, diversity, developability, and provide efficient time frames to identify lead candidate antibodies.
Importance of library size
A key characteristic that the latest generation of antibody libraries seeks to achieve is diversity. High diversity is created by engineering vast libraries containing billions of unique sequences. The correlation between library size and diversity is not implicit. Within the finite space of a sizeable library not all sequences will encode a functional antibody or antibody fragment; therefore, ensuring that the functional size of the library is significant (i.e. >80% of the whole library) is a pivotal step in its development. One of the ways scientists can achieve this is by reducing sequence motifs that cause developability liabilities of lead candidates and hence avoiding loss of interesting candidates later in the development process.
Bio-Rad’s new best-in-class platform
Bio-Rad’s Pioneer Antibody Discovery Platform is an innovative solution to biologics discovery. At the heart of the Pioneer Platform is its library, designed to maximize diversity and developability of lead candidates. The Pioneer phage display library was bioengineered to include more than 200 billion unique sequences with high functionality (functional sequences at ~90% of whole library size) and minimize sequence liabilities. Combined with Bio-Rad’s new, proprietary display technology (SpyDisplay) which simplifies selection of candidates through a seamless workflow, the platform achieved its aims: highly diverse and functional. Early data on topical check point inhibitors confirm the design of the library is on target with the identification of unique candidates but importantly dissimilar sequences with varying CDR lengths and sub-nanomolar affinities.
Given the development of biologics is inherently complex, working with Bio-Rad in the discovery phase offers time and cost benefits. Get in touch to learn more on how Bio-Rad’s Pioneer Antibody Discovery Platform can support you to meet your demands for high quality leads.
1. Cercek, Andrea, et al. “PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer: Nejm.” New England Journal of Medicine, 23 June 2022, https://www.nejm.org/doi/full/.