PEGS Boston 2021 Recap Series

Structure Knowledge is Vital for Design and Development of Better Therapeutics

In today’s RECAP: PEGS Boston 2021 series, we discuss Dr. Olga Ab’s talk on an important class of therapeutics in the fight against cancer, and highlight why Rapid Novor seeks to empower scientists with full antibody protein sequences.

Olga Ab – Targeting Folate Receptor Alpha (FRα) with IMGN151, a Next-Generation Antibody-Drug Conjugate (ADC)

Dr. Ab’s presentation was a clear and concise presentation on how to fine tune antibody-drug conjugates (ADCs) to develop more potent and precise treatments against cancers. With a focus on developing better treatments, Dr. Ab’s team at ImmunoGen Inc., chose to focus on folate receptor alpha (FRα) due to its high expression in cancers like ovarian cancer, which is linked to a high mortality rate.

Internal research demonstrated that FRα expression was highly dysregulated (high heterogeneity) in ovarian cancer cells from patients. Though they had developed a previous therapeutic (MIRV), they sought to improve MIRV’s properties to increase binding, cellular internalization, processing efficiency, and half-life, given their findings on heterogeneity. With these properties in mind, they designed IMGN151 as a biparatopic antibody keeping MIRV sequences and introducing an scFcv to target another FRα epitope and adding to the body a linker to improve structure stability, and thus half-life. These changes resulted in a therapeutic with better binding, internalization, and cytotoxic activities compared to its predecessor in vitro, in vivo (monkeys) and ex vivo (cells from xenografts from patients).

Why does the primary amino acid sequence matter?

Dr. Ab’s presentation was an important reminder on how knowing the primary amino acid sequence is crucial to understanding therapeutic stability and activity. The primary aa sequence can also be used to further characterize the structure by generating recombinants in higher yields to allow researchers to perform pesky experimental work such as cryo EM. Such has been the case with two of our clients in the development of neutralization antibodies against important emerging diseases, and in the characterization of brain proteins. Without it, manipulations of the sequence such as those spoken by Dr. Ab would not be possible. Whether you want to confirm the primary sequence of your therapeutic leads, or uncover novel targets, Rapid Novor is here to help you. Contact us so we can discuss how next generation protein sequencing can best suit your pipeline needs.

Next in the PEGS Boston 2021 Recap Series…

Stay tuned, we’ll be talking about Polyclonal Antibody Sequencing next. Sign up for our Rapid Insights to get a recap of the whole series.