Discovery

Amplifyer Bio humanized priming agent boosts ctDNA recovery up to 100-fold in mice

Amplifyer Bio humanized priming agent boosts ctDNA recovery up to 100-fold in mice

Amplifyer Bio, an MIT and Broad Institute spinout developing agents designed to increase the amount of circulating tumor DNA (ctDNA) recoverable from blood, reported preclinical data showing that a humanized DNA-binding antibody achieved up to a 100-fold increase in ctDNA recovery in tumor-bearing mice.

The Cambridge, Massachusetts-based company presented the findings at the 2026 ctDNA International Symposium following the design and screening of 74 humanized DNA-binding monoclonal antibodies. Multiple candidates produced greater than 20-fold increases in ctDNA recovery two hours after administration, while one candidate achieved an increase of up to 100-fold, according to Amplifyer.

The new candidates build on liquid-biopsy research originating in the laboratories of Sangeeta Bhatia and J. Christopher Love at the Massachusetts Institute of Technology (MIT) and Viktor Adalsteinsson at the Broad Institute of MIT and Harvard. Bhatia, Love, and Adalsteinsson are co-founders of Amplifyer, and the company was spun out of MIT and the Broad Institute to develop the priming-agent technology.

The underlying approach seeks to address a biological limitation of liquid biopsy testing: ctDNA released by tumors can occur at very low concentrations and is rapidly cleared from circulation. Administering a DNA-binding priming agent before blood collection can transiently slow that clearance, increasing the amount of cell-free DNA (cfDNA), including tumor-derived DNA, available for analysis.

Earlier academic work from the MIT and Broad teams demonstrated the priming concept using a monoclonal antibody, establishing that cfDNA clearance could be transiently reduced to improve recovery of tumor DNA. More recent work from the researchers, posted as a bioRxiv preprint in January 2026, investigated the molecular determinants of antibody-mediated priming.

That study was led by researchers including Shervin Tabrizi, Claire Sullivan, Kasturi Chakraborty, and Amplifyer founding scientist Carmen Martin-Alonso, with Bhatia, Adalsteinsson, and Love among the senior authors. The work involved the Koch Institute for Integrative Cancer Research at MIT and the Broad Institute, alongside researchers affiliated with Mass General Brigham, Harvard Medical School, the Harvard-MIT Division of Health Sciences and Technology, the University of Pennsylvania, and other institutions.

The researchers found that antibodies targeting double-stranded DNA and mononucleosomes could increase ctDNA concentrations, with high avidity for double-stranded DNA associated with stronger priming activity. The Fc antibody domain was not required for the effect, while engineered non-immunoglobulin DNA-binding agents also demonstrated priming activity, suggesting that the mechanism could potentially support multiple molecular designs.

The earlier January study did not, however, report the same humanized-candidate dataset disclosed by Amplifyer in September. The company described the latest results as the first demonstration of one of its humanized priming agents increasing ctDNA recovery in vivo and said the effect sizes exceeded those obtained with the earlier academic antibody.

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In the new experiments, Amplifyer also reported that priming improved cancer-detection sensitivity using a 16-probe panel and enabled more comprehensive molecular profiling. Binding to cfDNA was observed across a range of human cancer cell lines, supporting a potentially tumor-agnostic mechanism. Whole-genome sequencing showed that some candidates preserved cfDNA fragmentomic features without introducing GC bias, an important consideration if increasing DNA recovery is to remain compatible with downstream sequencing analyses.

The company did not disclose full quantitative results for the antibody screen, including median ctDNA recovery, dose-response relationships, confidence intervals, or other statistical parameters. The reported 100-fold increase represents an “up to” value rather than a typical effect across the candidate series. Amplifyer also said only some candidates preserved cfDNA fragmentomic characteristics, suggesting candidate selection must account for DNA quality as well as the magnitude of recovery.

The experiments remain preclinical. The humanized agents were evaluated in tumor-bearing mouse models, with ctDNA recovery assessed approximately two hours after intravenous administration, and Amplifyer did not disclose toxicology or broader safety data in announcing the results. The September findings have also not been reported in a peer-reviewed publication.

Amplifyer said the results will allow it to advance a lead priming agent into clinical development. The company identifies its first program as AMP-001, a monoclonal antibody designed to bind cfDNA and transiently protect it from clearance before a blood draw. It has not publicly disclosed an IND filing date or detailed timeline for IND-enabling studies.

If the approach translates to humans, priming could complement rather than replace existing liquid-biopsy assays by increasing the amount of tumor-derived DNA available upstream of sequencing or other analytical platforms. Potential applications include minimal residual disease monitoring, therapy selection, disease monitoring, and early cancer detection, where low ctDNA abundance can limit assay sensitivity.


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