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.