Abstract
We developed a potentially novel and robust antibody discovery methodology, termed selection of phage-displayed accessible recombinant targeted antibodies (SPARTA). This combines an in vitro screening step of a naive human antibody library against known tumor targets, with in vivo selections based on tumor-homing capabilities of a preenriched antibody pool. This unique approach overcomes several rate-limiting challenges to generate human antibodies amenable to rapid translation into medical applications. As a proof of concept, we evaluated SPARTA on 2 well-established tumor cell surface targets, EphA5 and GRP78. We evaluated antibodies that showed tumor-targeting selectivity as a representative panel of antibody-drug conjugates (ADCs) and were highly efficacious. Our results validate a discovery platform to identify and validate monoclonal antibodies with favorable tumor-targeting attributes. This approach may also extend to other diseases with known cell surface targets and affected tissues easily isolated for in vivo selection.
Authors
Sara D’Angelo, Fernanda I. Staquicini, Fortunato Ferrara, Daniela I. Staquicini, Geetanjali Sharma, Christy A. Tarleton, Huynh Nguyen, Leslie A. Naranjo, Richard L. Sidman, Wadih Arap, Andrew R.M. Bradbury, Renata Pasqualini
Figure 5
Cytotoxic profile of anti-EphA5 and anti-GRP78 monoclonal antibodies.
