Case Study: Single Chain Antibodies
Find small and sleek single domain antibodies for next-gen antibody therapies
HcAbs are single chain antibodies lacking light chains, found naturally in camelids such as llamas and alpacas (along with conventional paired heavy and light chain IgG antibodies, at approximately 50% frequency). HcAbs are valuable for various antibody-based therapeutics, such as bispecific antibodies, antibody-drug conjugates and CAR-Ts. In addition, the decreased complexity of having only single chains comprising the antibody molecules means they are more straightforward to produce and manufacture.
The Challenge: A partner needed to identify HcAbs from immunized llamas against transforming growth factor beta-3 (TGF-ß3) that could also discriminate between closely-related homologs, transforming growth factor beta-1 (TGF-ß1) and transforming growth factor beta-2 (TGF-ß2). The partner did not have the screening technology to identify antibodies with such restricted specificity.
Our Approach: We designed custom reagents to distinguish HcAbs from conventional IgGs in llamas and also designed custom assays to identify HcAbs specific to TGF-ß3 that could differentiate between TGF-ß1 and TGF-ß2. To find these rare antibodies, we deployed our deep screening platform and screened approximately 20 million single cells over four days to deeply mine the immune response.
The Result: We identified 67 unique HcAbs, which is a <0.001% antigen specific HcAb hit frequency, indicating an exceedingly rare antibody. This illustrates the flexibility of our platform to discover non-conventional antibody modalities, from alternative species, and the depth required to find rare antibodies with very specific properties.
Find out how our single domain discovery technology can give you the flexibility to take on tough challenges by contacting our team.