The paper describes a new approach to engineer antibodies to act as agonists for cell surface receptors, which has potential applications in developing new biotherapeutics. The authors developed a method to re-shape conventional Y-shaped antibodies into more compact, linear “i-shaped” antibodies (iAbs) by transplanting sets of mutations identified in naturally occurring broadly neutralizing antibodies against HIV. Adding a new approach to the antibody engineering tool box — iAb engineering.
Three sets of mutations termed iAbdx, iAbaff1, and iAbaff2 were engrafted into panels of 10 antibodies targeting OX40 and induced the iAb shape, as confirmed by negative stain electron microscopy.