Case Study: Amplifying Antibody Diversity

by AbCellera

Case Study: Amplifying Antibody Diversity

The Challenge:

A discovery program to identify an antibody against a validated human target, with 100% homology across mice, rats and humans.

Accessing a diverse set of antibodies was a must. In addition, the human target had two related protein homologs, against which antibodies had to be carefully screened.

Our Approach:

In this campaign, we deployed our optimized immunization protocols to generate a robust immune response in humanized rodents.

Next, we developed a high throughput single-cell screening strategy that used multiplexed fluorescence detection to find antibodies specific to the target, but also with binding profiles that would cross-react with the closely related targets.

The Result:

We screened four million single cells from immunized rodents and identified more than 1,900 target-specific antibodies, a hit-frequency that demonstrates a robust immune response from breaking tolerance against a 100% homologous target.

Of these hits, we identified 428 unique antibody leads with a degree of somatic hypermutation that indicates a mature and directed immune response against a difficult target. We also performed immune repertoire sequencing in parallel and identified clonal lineages in Celium™.

Read the full case study at https://www.abcellera.com/post/amplifying-antibody-diversity