In May, a leading provider of precision medicine laboratory services, CellCarta, acquired the commercial rights to the CPTAC-qualified antibody panels and assays developed by the Paulovich laboratory at Fred Hutchinson Cancer Center; they produce high-end multiplex quantitative immuno-MRM mass spectrophotometry-based assays for pharmaceutical and biotech industry partners.
In response, CPTAC is proud to present an interview with Dr. Amanda Paulovich. Dr. Paulovich is a professor in both the Clinical Research Division at Fred Hutch and the University of Washington School of Medicine’s Division of Oncology, and she holds the Aven Foundation Endowed Chair. Here, she highlights the arc of her own career, what inspires her, why precision oncology is important, and the significance of the CellCarta partnership.
Can you briefly trace the trajectory of your career?
As a young oncologist treating cancer patients, I was struck by the paucity of assays for measuring clinically relevant phenotypes in my patients, and the limitations that this put on my ability to practice what we now call “precision oncology.” One patient’s tumor would melt away with standard of care therapy, whereas another patient with what appeared to be the same tumor would nonetheless experience disease progression on the same therapy. This inter-patient variation both fascinated and frustrated me. Having been trained as a geneticist, I realized that the full spectrum of phenotypic diversity seen in my patients could not be deciphered based on genomic data alone (especially not single gene markers), and that having the ability to quantify proteins- especially networks of proteins- would add value. Although proteins are critical executors of our physiology and the targets of most modern therapies, most human proteins cannot be reliably quantified in the clinical lab (especially in multiplex), and thus the human proteome remains largely clinically inaccessible. Realizing that the proteome is going to be an essential complement to the genome, in 2003 I joined Fred Hutch and established a translational, interdisciplinary mass spectrometry (MS) research group with the goal of optimizing & standardizing modern proteomic methods & approaches to lay the groundwork for applying proteomics in a robust fashion to translational & clinical research to support precision oncology. In 2004-2005, I spearheaded one of two NCI teams that generated the data that laid the groundwork for the creation of the NCI-CPTAC Program.
How would you describe the type of work your lab does and its importance to someone who is not familiar with it?
I am fortunate to have a core group of fantastic colleagues in my laboratory at Fred Hutch with multidisciplinary expertise, including analytical chemistry, bioinformatics, biochemistry, biology, and oncology. For the past 18+ years, our research has focused on helping to solve the problem that the human proteome is largely clinically inaccessible, through building methods and reagents for analytically robust, multiplex quantification of proteins using mass spectrometry. Being able to measure proteins reliably (and in multiplex) in the clinical setting is essential for advancing precision oncology, since most modern drugs measure proteins and since tumor response to therapy is a complex trait that usually can’t be reliably predicted using single gene/single protein assays. Our laboratory, which is now a CLIA environment, works to advance an enabling protein assay platform (multiple reaction monitoring mass spectrometry, MRM) to: (i) translate MRM-based proteins assays into clinical trials (via our CLIA targeted proteomics lab), (ii) translate MRM-based assays into clinical reference labs, and (iii) lay the groundwork for translation of MS-based protein assays into a regulated space. My laboratory has developed and validated >1,700 MRM-based protein assays and >500 custom monoclonal antibodies targeting cancer-relevant proteins. All our assays, antibodies, and validation data are made broadly available to the research community via NCI-CPTAC’s Antibody and Assay Portals. Recently, CellCarta acquired Fred Hutch’s commercial rights to our collection, and soon will provide an industrialized platform to help democratize access to the mass spectrometry-based protein assays we have developed under the CPTAC Program.
Can you provide a perspective on the significance of the CellCarta partnership?
My academic laboratory at Fred Hutch has been the major site of deployment of the assays we have developed. Because MRM is not yet widely available and requires specialized mass spectrometry infrastructure and expertise, the impact of distribution of antibodies and assays via the CPTAC Antibody and Assay portals has been limited to expert labs, since most potential end users do not have the expertise and/or access to the mass spec infrastructure to run the assays. Furthermore, the assays require incorporation of additional reagents (e.g., stable isotope labeled internal standards), which the typical end user does not have in hand, and which would be cost prohibitive to generate for most projects, especially for highly multiplexed MRM assay panels. For these CPTAC assays to realize their full impact to biomedical research, access must be democratized, including for organizations without expertise in mass spectrometry. This is a critical unmet need, because a high percentage of biomedical research requires the ability to quantify proteins, but most scientists do not have expertise or capabilities to run MS-based assays. Thus, it is imperative to make available a commercial service that democratizes access.
As mentioned above, CellCarta recently acquired the exclusive commercial license to Fred Hutch’s rights to commercialize the CPTAC-qualified assays we have developed, with the intent to industrialize and deploy multiplex MRM-based protein assay panels at scale and within the regulatory framework required by pharmaceutical and biotechnology companies looking to leverage this technology for their drug developments efforts, including mechanism of action studies, pharmacodynamics, and patient stratification- this should increase the likelihood of success for new clinical assets and hopefully improve patient outcomes. CellCarta (formerly Caprion Biosciences) has its roots as an MRM-based company, making them an ideal partner for deploying the assays. We’ll be working closely with the CellCarta mass spec team in the coming months to ensure that the assays are successfully implemented.
Any final thoughts?
Cancer phenotypes are complex traits, and accurately predicting durable responses to therapies will rarely be achieved through the current model of single gene/single protein predictive biomarkers. To truly move precision oncology ahead, we need to develop approaches to capture the complexity of clinical phenotypes. NextGen molecular diagnostics will be multianalyte panels combined with clinical features in algorithmic-driven patient care. Proteomic technologies are mature to support multianalyte panel-based diagnostics, from discovery through to implementation in clinical laboratories. Institutional, financial, and regulatory hurdles are impeding progress, and I hope we can break through some of these barriers in the coming years--patients are counting on it.