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Mining for novel antibodies: Retrogenix aids assessment of specificity


A recent study, led by The Scripps Institute in Florida, demonstrates the successful generation of an extensive phage display library of rabbit monoclonal antibodies (mAbs) which can serve as a rich source of new mAbs with potential research, diagnostic and therapeutic uses. The paper, which was co-authored by scientists at Retrogenix, also provides an example of the utility of the Retrogenix technology in off-target profiling of antibodies.

The group developed a first-in-kind naïve rabbit antibody library which is unbiased towards the recognition of any particular human antigen or epitope. They then validated it by investigating panels of antibodies selected against targets which have potential utility in cancer therapy.

A total of 25 antibodies for two bait targets, ROR1 and ROR2, were extensively characterized during the project. The 13 rabbit anti-human ROR1 mAbs and the 12 rabbit anti-human ROR2 mAbs that were selected showed a high degree of diversity in amino-acid sequence, affinity and epitope binding. None were cross-reactive between human ROR1 and ROR2, whereas 8 of the mAbs also bound to the respective mouse ortholog, making them particularly attractive for preclinical investigations in mouse models.

The researchers then selected one of each of the ROR1 and ROR2 antibodies for further investigation as potential antibody-based therapeutics. Using Retrogenix’s cell microarray technology, the two antibodies were screened for potential off-target binding against approximately 4,300 over-expressed human plasma membrane proteins and found to be highly specific to their respective targets. Further examination as potential cancer therapies in the chimeric CAR T format provided additional evidence that support these antibodies as highly attractive candidates for clinical translation.

This paper highlights the potential value of mining a library of >10 billion independent antibodies in order to bypass immunisation and accelerate the discovery of novel rabbit mAbs against antigens of interest. For a link to the abstract and full text options please click here.

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