ActivMAb^® Antibody Discovery Platform

The ACTIVMAb^® discovery platform represents one of only a handful of major platforms for human antibody discovery. Libraries of immunoglobulin heavy and light chain genes are cloned into the vaccinia virus genome using proprietary Vaccinex technology. Mammalian cells are co-infected with separate heavy and light chain recombinants and cell clones expressing specific antibody are efficiently selected through magnetic bead technology and high speed cell sorting. Because heavy and light chain libraries remain separate throughout library construction and antibody selection, we are able to achieve very high combinatorial diversities from libraries with 10⁷ independent heavy and light chain genes. Our technology offers advantages not readily available in other platforms. In contrast to phage display, our antibodies are selected in mammalian cells with full post-translational modifications including glycosylation. As an in vitro library-based method, the Vaccinex technology is not subject to limitations of repertoire imposed by in vivo tolerance as in immunoglobulin transgenic mice. In comparison to antibody humanization, Vaccinex antibodies are not only fully human but allow selection of a panel of antibodies with related specificity and expressing diverse immunoglobulin variable region families to enrich lead selection.

Separate libraries of heavy and light chains make it possible to readily convert mouse antibodies to fully human antibodies with similar epitope specificity by screening directly with either mouse heavy or light chain into the corresponding partner human library. For example, a chimeric mouse heavy chain variable region with human constant region is employed to screen a library of human light chains and then the selected fully human light chains are used to screen a library of human heavy chains. Moreover, antibodies selected from initial screens can be improved upon through an affinity maturation strategy involving the exchange of heavy and/or light chain against the partner library or through random mutagenesis of CDR sequences followed by creation and re-screening of specific recombinant libraries.

Figure 1. The ACTIVMAb^® discovery platform has been very successful at identifying multiple antibodies with diverse heavy and light chains against a variety of target antigens.