PEGS 2017:

    Poster: Site-Specific Conjugation to a Native Lysine in IgG by Microbial Transglutaminase

RESPECT Publications:

    Cancer Biology & Therapy Journal Article: The conjugation of toxins, dyes, peptides, or proteins to monoclonal antibodies is often performed via free thiol groups generated by either partial reduction methods or engineering free cysteine residues into the antibody sequence. Antibodies from the rabbit Oryctolagus cuniculus have an additional intrachain disulfide bond, whereby the light chain variable kappa domain is bridged to the constant kappa region between cysteine residues at positions 80 and 171, respectively. Chimerization of rabbit antibodies with human constant domains allows for the generation of a free thiol group at the light chain position 80 (C80) that can be utilized for site-specific conjugation. An efficient process for the purification of highly conjugatable antibody was developed. The unpaired C80 was shown to be efficiently conjugated using a number of different maleimido-based ligands. REsidue SPEcific Conjugation Technology (RESPECT) antibody-drug conjugates prepared using rabbit-human chimeric anti-human mesothelin rabbit antibodies and maleimido-PEG2-auristatin conjugated to C80 were shown to be highly potent and specific in vitro and effective in vivo in reduction of tumor growth in a highly aggressive mesothelin-expressing xenograft tumor model.

AACR 2017:

  • Poster: RESPECT (REsidue-SPEcific Conjugation Technology): Platform technologies utilizing native cysteine and lysine residues for the generation of homogeneous antibody-drug conjugates

World ADC 2016:

  • Abstract and Poster: Residue-Specific Conjugation Technology (ReSpeCT) utilizing a native cysteine residue in the light chain of Oryctolagus cuniculus immunoglobulins
  • Abstract and Poster: Site-specific Conjugation to a Native Lysine in IgG by Microbial Transglutaminase