Madeline Repollet, Head of Clinical Laboratories at ANGLE North America
I had the pleasure of speaking to Madeline Repollet, Head of Clinical Laboratories at ANGLE North America. Madeline has more than 30 years of clinical lab experience, 21 of those in the liquid biopsy space. Madeline has years of global laboratory management experience working with clinical laboratories in the US, The Netherlands, Belgium, and Italy. She is the co-author in several CTC publications, holds multiple patents, and was a co-developer of the CellSearch® CTC definition, establishing the first CellSearch® training program and managing the clinical studies that led to its novel regulatory clearance.
Circulating tumor cells have been shown to have promising value in the clinical management of tumors; In your opinion, what place will CTC detection and Immuno characterization have in coming years in light of the many ctDNA based assays currently under development?
Detection and immuno characterization of CTCs can provide vital information from the population of tumor cells which have evaded elimination by treatment and/or the body’s immune system and escaped into the circulatory system. While ctDNA assays can provide some information on the tumor burden and its genotype, the DNA present in the sample comes from not only viable CTCs, but also from dead and/or dying CTCs as well as from other blood cells. ctDNA cannot provide any information with regards to a tumor’s phenotype. CTCs are complementary to ctDNA and can provide insight into the “real-time” phenotype and genotype of the active tumor using functional assays for proteins, DNA and RNA. Viable CTCs can also be cultured to enable drug resistance testing in vitro or in vivo. Detection and characterization of CTCs will provide more information compared to ctDNA alone.
” CTCs are complementary to ctDNA and can provide insight into the “real-time” phenotype and genotype of the active tumor”
Programmed death-ligand 1 (PD-L1) allows cancer cells to evade the host immune response when upregulated; How far are we from an IVD approved assay that provides clinically relevant information based on PD-L1 expression in CTCs?
I believe that we are very close to having an FDA-cleared assay for the detection of PD-L1 expression on CTCs. This is based on how many RUO assays and LDTs have been and currently are being developed for this indication, and also because immune checkpoint inhibitor drugs such as Keytruda require the use of a PD-L1 IHC assay on tissue to determine eligibility for the drug. Performing this test on CTCs from a blood sample instead of having to obtain a tissue sample for testing will allow for reduced risk to the patient, reduced costs, more accessibility, and enable the possibility for repeat testing/monitoring. Because CTCs represent the current status of the tumor, they may be a better, more accurate predictor of response to therapy.
The broad range of liquid biopsy utilization spans from screening, diagnosis, monitoring to targeted treatment selection; In your opinion, which of the potential indications will be more likely to become standard procedure for patient care and why?
I believe that treatment selection will be the first liquid biopsy indication to become a standard procedure for patient care. Liquid biopsies allow for easy access to tumor-related material (e.g. CTCs and DNA/RNA) that can be interrogated for biomarkers that will provide patient-specific information to enable personalized medicine to become more of a reality. Compared to the invasive procedures required for the procurement of a tissue sample, the safe sampling procedures for liquid biopsies will make monitoring of a patient’s response to therapy and their disease status a much easier process.
In the current times where healthcare encompasses 18% of the US GDP, reducing costs is crucial for new technologies to thrive and for patients to benefit. Access to healthcare at all economic levels is a known challenge, particularly in the US. The use of liquid biopsies significantly reduces the economical burden on the healthcare system and increases access to healthcare services for those who can’t afford expensive procedures.
” The use of liquid biopsies significantly reduces the economical burden on the healthcare system and increases access to healthcare services for those who can’t afford expensive procedures. “
Based on your experience, what are the key elements required to introduce a CTC-based assay into the clinical routine?
Circulating Tumor Cells have been an interesting topic in medicine since the late 1800’s, yet the difficulties in establishing robust and reproducible technologies that enable the capture and interpretation of CTCs have delayed their use in patient management. Roger’s diffusion of innovations theory can explain this, with innovators or early adopters (a.k.a key opinion leaders like researchers in the CTC academia) leading the studies of CTC technologies and with physicians as the later adopters of the technology because they need to be able to understand and interpret the results so they can incorporate them into clinical practice. In relation to routine laboratory testing, CTC assays must be reproducible, accurate, precise, and reportable.
Key elements for the introduction of CTC technologies into the clinical routine include dissemination of knowledge (education) on the technologies and usefulness for patient management, development of robust assays to ensure consistency in results, and establishment of clinical validity and clinical utility data.
