Generation of monoclonal antibodies targeting tumor-associated glycoproteins

Funding format: ProFIT („Programm zur Förderung der Forschung, Innovationen und Technologien“)

Project partners:

• Fraunhofer Institute for Cell Therapy and Immunology, Branch Bioanalytics and Bioprocesses, Potsdam-Golm (IZI-BB),
  Department of Cell-free and Cell-based Bioproduction / Cell-free Protein Synthesis
• YUMAB GmbH

Goals: 

• Generation of monoclonal antibodies (mAbs) targeting combined epitopes comprising tumor-related proteins and their tumor-specific glycosylation
• Generation of monoclonal IgG1 antibodies by phage-display technology incl. human antibody libraries using different antigens and reference materials
• Antibody screening, identification of lead candidates and format optimization (bispecifics, immunocytokines and antibody-drug-conjugates) for improved efficacy by use of cell-free and cellular production technologies

Expected results:

• Identification of optimal work-flows for antigen generation with subsequent phage-display / panning for selection of antibodies
• Generation of new antibodies targeting O-glycopeptide mixed epitopes with the following advantages:

Characteristics	Protein-specific mAb	Glycan-specific mAb	Glyco-protein (mix) epitope-specific mAb
High tumor specificity	X	√	√
High number of binding sites per cell	X	√	√
High affinity	√	X	√
Signaling function	√	X	√
Impact on tumor progression	√	√	√
Expression on tumor stem cells	√	√	√

• New lead candidates combining high binding affinity and tumor specificity for improved safety as well as high anti-tumor efficacy available for further development in oncology