Abstract
We developed a potentially novel and robust antibody discovery methodology, termed
s
election of
p
hage-displayed
a
ccessible
r
ecombinant
t
argeted
a
ntibodies (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.
Selection of Phage-Display Accessible Recombinant Targeted Antibodies (SPARTA) generate fully functional human recombinant monoclonal antibodies capable of targeting tumors in vivo.