In this webinar, you will learn:

  • Non-Invasive Liquid Biopsies: Cell-free DNA as a key analyte for non-invasive liquid biopsies for cancer diagnosis and monitoring.
  • Enhanced Cell-Free DNA Recovery: Strategies to improve cell-free DNA recovery, including the use of DNA priming agents like DNA-binding monoclonal antibodies.
  • Fc-Domain Engineering: The process of engineering the Fc-domain of antibodies to modify FcγR interactions, enhancing the effectiveness as DNA priming agents.
  • Antibody Sequencing and Engineering: How de novo antibody sequencing informs the engineering of monoclonal antibodies, optimizing their performance for specific applications.

Circulating tumor DNA (ctDNA), released into the bloodstream by tumor cells, is a promising biomarker for cancer detection, offering noninvasive diagnosis and disease monitoring through standard blood tests. However, the utility of cell-free DNA (cfDNA) is constrained by its scarcity, caused by degradation by circulating nucleases and organ-mediated clearance.

To enhance the sensitivity of ctDNA detection in liquid biopsies, attenuating cfDNA clearance becomes crucial. This can be achieved by employing DNA-binding agents. Monoclonal antibodies (mAbs) that bind directly to cfDNA serve as a DNA priming agent, offering protection from circulating DNAases and extending its half-life in circulation. The application of mAbs as DNA-priming agents significantly boosts ctDNA recovery from the blood by more than 10-fold. This effectively overcomes the limitation of low ctDNA quantities that often restrict the sensitivity of liquid biopsies for oncological purposes.

Antibody Sequencing Enables Fc-Engineering of DNA-Binding Antibodies

De novo antibody sequencing enables the engineering of the Fc-domain of the mAb priming agent, eliminating Fc gamma receptor (FcγR)-mediated clearance, and enhances ctDNA recovery. A comprehensive understanding of the amino acid sequence facilitates informed engineering, allowing for the modification of amino acid sequences to introduce desired antibody functions.

Speaker Bios