3RA7

Bispecific digoxigenin binding antibodies for targeted payload delivery

Summary for 3RA7

• Entry DOI: 10.2210/pdb3ra7/pdb
• Descriptor: Fab fragment, light chain, Fab fragment, heavy chain, DIGOXIGENIN, ... (4 entities in total)
• Functional Keywords: fab fragment, antibody engineering, cancer, targeted payload delivery, immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 4
• Total formula weight: 96709.96

Authors

Hopfner, K.P.,Lammens, A. (deposition date: 2011-03-27, release date: 2011-07-20, Last modification date: 2024-10-16)

Primary citation

Metz, S.,Haas, A.K.,Daub, K.,Croasdale, R.,Stracke, J.,Lau, W.,Georges, G.,Josel, H.P.,Dziadek, S.,Hopfner, K.P.,Lammens, A.,Scheuer, W.,Hoffmann, E.,Mundigl, O.,Brinkmann, U.
Bispecific digoxigenin-binding antibodies for targeted payload delivery
Proc.Natl.Acad.Sci.USA, 108:8194-8199, 2011

PubMed Abstract: Bispecific antibodies that bind cell-surface targets as well as digoxigenin (Dig) were generated for targeted payload delivery. Targeting moieties are IgGs that bind the tumor antigens Her2, IGF1R, CD22, or LeY. A Dig-binding single-chain Fv was attached in disulfide-stabilized form to C termini of CH3 domains of targeting antibodies. Bispecific molecules were expressed in mammalian cells and purified in the same manner as unmodified IgGs. They are stable without aggregation propensity and retain binding specificity/affinity to cell-surface antigens and Dig. Digoxigeninylated payloads were generated that retain full functionality and can be complexed to bispecific antibodies in a defined 21 ratio. Payloads include small compounds (Dig-Cy5, Dig-Doxorubicin) and proteins (Dig-GFP). Complexed payloads are targeted by the bispecifics to cancer cells and because these complexes are stable in serum, they can be applied for targeted delivery. Because Dig bispecifics also effectively capture digoxigeninylated compounds under physiological conditions, separate administration of uncharged Dig bispecifics followed by application of Dig payload is sufficient to achieve antibody-mediated targeting in vitro and in vivo.

PubMed: 21536919
DOI: 10.1073/pnas.1018565108

Experimental method

X-RAY DIFFRACTION (2.798 Å)