CMC Activities For Biologics and Monoclonal Antibodies

CMC Activities For Biologics and Monoclonal Antibodies

CMC Activities For Biologics, GenScript ProBio has partnered with single-cell technology company Berkeley Lights, Inc. to offer the innovative Optofluidic-based Beacon (r) platform at our South San Francisco laboratory. The Beacon(r), platform’s nanochip technology allows for the functional analysis of antibodies secreted by single B cells. The Berkeley Lights technology allows for a faster antibody discovery process than the traditional hybridoma approach.

We used the Beacon(r), a platform that screens single plasma cells for antibodies against PD-1. After an 8-week vaccination, we immunized Balb/c animals with recombinant Fc fusion human PD-L1extracellular domain (ECD). We also isolated CD138+ plasma cells from bone marrow.

For analysis, plasma B cells were taken from the spleen and bone marrow. A variety of assays were run simultaneously, including cell-based binding to CHOK1 cells engineered with high levels of human PD-1 and cell-based blocking using PD-1.

These essays were written on the Beacon and allowed the identification of approximately 250 antibodies that bind to PD-1L1. Nearly 20% of these antibodies blocked PD-1 from PD-1L1 cells.

Interestingly, the majority of PD-1 specific blocking antibodies were identified in plasma B cells taken from bone marrow. However, the yield from bone marrow plasma cells was less than 20% than that from the spleen. The Beacon(r), which was responsible for sequence recovery, exported single plasma B cells.

After reverse-transcription, amplification, and single plasma B cell sequencing by NGS, we evaluated the sequence diversity of anti-PD-L1 antibody hits, most of which were divergent across multiple residues in CDR3. We identified more than 40 cell-based binding or blocking antibodies after analyzing over 30,000 single plasma cells. These are currently being sequenced cloned and further characterized.

Our results from plasma cell cloning using the Beacon(r), revealed that plasma cells can produce functional antibodies candidates in a matter of hours, compared to the 8-12 weeks required for the standard hybridoma campaign. This significantly accelerates the process of antibody discovery. This technology can also be used to quickly compare immunization strategies and mouse strains to identify B cells that could be isolated to maximize the recovery of functional antibodies.

Take a closer look at this poster that was presented at the 2018 Antibody Engineering & Therapeutics conference.

GenScript ProBio Beacon(r), platform expands its broad antibody discovery capabilities and allows for greater access to the immune repertoire. Our global clients now have more options for finding the therapeutic antibody candidates they are looking for.

GenScript ProBio offers large molecule CMC testing

With team of experienced scientists and proprietary development platform, GenScript ProBio can perform many of the CMC requirements necessary for obtaining a license for a Biopharmaceutical. We also offer a thorough analysis of growth rate, subcultivation ratios, cell mass, and other parameters. GenScript has chambers that are suitable for ICH conditions and a robust stability program.

The analytical and bioanalytical laboratories can conduct identity, purity, and strength testing of large molecules. The microbiology section can perform sterilization validations, endotoxin tests, container closure testing, and other USP microbiology testing. Contact GenScript ProBio to learn how we can assist your company in meeting its Biologics CMC needs.

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