Mabfilin and Fabfilin - New antibody-scaffold fusion formats for multispecific targeting concepts

Abstract

Protein based binding molecules have a broad applicability from therapeutic to technical use. Monoclonal antibodies represent the major class of this type of agents complemented by innovative approaches using scaffold proteins with tailor-made properties. Various concepts for new formats combining antibody chains or antibody fragments and fusions with other entities have been developed recently. This strategy opens up options to design molecules with biophysical, biochemical and pharmacological characteristics in a broad range while simultaneously addressing several targets or epitopes. The demand for such compounds is still growing as reflected by the literature and further new ideas are expected. In this context we developed so called Mabfilin and Fabfilin molecules. The formats synergistically bring together the classical antibody or fragments thereof supplemented with additional binding moieties, the Affilin molecules. These are based on the scaffold ubiquitin endowed with novel targeting properties by local randomization and selection from combinatorial libraries. Mab-/Fabfilin variants show advantageous biochemical properties and open a new route for the development of multispecific compounds for flexible applications.

Almost 50 Years of Monomeric Extracellular Ubiquitin (eUb)

“…Because Ub does not have post-translational modifications, it may be easily obtained in a recombinant form in bacteria [ 167 ]; its poor half-life in circulation, however, might be one of its drawbacks—this could need linking to other proteins, like Fc or BSA [ 167 ]. To overcome these restrictions, Affilin ® has also been employed in combination with antibodies and fab in various forms as a bispecific molecule and pair to adenoviral vectors [ 168 , 169 ]. Multiple targets focused on cancer therapy have been evaluated; however, their in vivo evaluation is still necessary.…”

Almost 50 Years of Monomeric Extracellular Ubiquitin (eUb)

“…Because Ub does not have post-translational modifications it may be easily obtained in a recombinant form in bacteria [161], its poor half-life in circulation, however, might be one of its drawbacks, this could need linking to other proteins, like Fc or BSA [161]. To get over these restrictions, Affilin ® has also been employed in combination with antibodies and Fab in various forms as a bispecific molecule and pair to adenoviral vectors [162,163]. Multiple targets focused on cancer therapy have been evaluated; however, it's in vivo evaluation is still necessary.…”

Protein scaffolds: antibody alternatives for cancer diagnosis and therapy

“… 176,177 Moreover, HER2 and EGFR binding affilins fused to the anti-EGFR monoclonal antibody cetuximab have been shown to achieve bi-specificity and strong inhibition of cancer cell proliferation in vitro . 178 …”

“…176,177 Moreover, HER2 and EGFR binding affilins fused to the anti-EGFR monoclonal antibody cetuximab have been shown to achieve bi-specificity and strong inhibition of cancer cell proliferation in vitro. 178 ADAPT. The albumin-binding domain with good solubility generally extends the half-life of drugs or probes.…”