TEST:

Parsortix Liquid Biopsy

Notably, when MDA-MB-231 cells spiked (i.e. supplemented) into DLA aliquots were processed using DanioCTC, cell dissemination patterns remained consistent. Successful xenografting of CTCs from a MBC patient revealed their primary localization in the head and trunk regions of zebrafish embryos.DanioCTC represents a major step forward in endeavors to study the dissemination of individual and rare patient-derived CTCs, thereby enhancing our understanding of metastatic breast cancer biology and facilitating the development of targeted interventions in MBC.

"ANGLE plc...is pleased to announce its participation at the 2024 Annual Congress of the European Association for Cancer Research (EACR 2024) being held in Rotterdam, Netherlands from 10 to 13 June 2024."

This study identified potentially actionable biomarkers in CTCs enriched using the Parsortix system, from cancer patient samples. Analysing the genetic profile of both CTCs and cfDNA, concomitantly, has the potential to better guide personalised treatment selection and monitoring of therapeutic response outcomes.

PD-L1, PIM-1 and AXL expression in CTCs indicate a potential benefit of targeted therapies for NSCLC patients who relapse following οsimertinib treatment.Conclusion Our results indicate the importance of complementary information obtained through parallel analysis of CTC and ctDNA. Comprehensive LB analysis efficiently represents the heterogeneous molecular landscape and provides prominent information on subsequent treatments for NSCLC patients progressing with osimertinib based on different druggable molecular alterations.

In the prostate cancer cohort, the presence of DDR+ CTCs was associated with response to treatment in 50% of the cases as reported at the time of blood draw, compared to 22% for DDR- CTCs (p<0.0001). A similar correlation was not observed in the ovarian cohort (p=0.69).Conclusion This research study demonstrates the ability to determine DDR status of CTCs isolated from a liquid biopsy using the Parsortix® system, highlighting it as a non-invasive tool to provide valuable insight into the efficacy of cancer therapies.

"ANGLE plc...is delighted to announce the publication of a study using the Parsortix® system to identify markers present in CTCs harvested from metastatic mutant-p53 platinum-resistant ovarian cancer (PROC) patients. The study was conducted as an offshoot of the European multi-centre GANNET53 Phase II clinical trial (NCT02012192) funded by the EU 7th Framework Programme (Grant agreement ID: 602602). The study investigated the efficacy of ganetespib in combination with paclitaxel vs. paclitaxel alone. Patients were enrolled across 12 clinical centres in Germany, Belgium, France, and Austria."

"ANGLE plc...is delighted to announce that it has signed a supplier agreement to develop a Parsortix-based Androgen Receptor1 (AR) detection assay for use in prostate cancer studies. The supplier agreement reported here is with AstraZeneca...This follows an earlier agreement to develop a methodology for CTC micronuclei detection using the Company's DNA Damage Response (DDR) assay, announced on 24 April 2024."

"ANGLE plc...has signed a supplier agreement with the global biopharmaceutical company, AstraZeneca PLC, to develop and validate a methodology leveraging ANGLE's existing DNA damage response ('DDR') assay for the detection of micronuclei in CTCs as a measure of DDR."

"ANGLE plc...announce its participation at the American Association for Cancer Research (AACR) Annual Meeting, San Diego, US between 5 to 10 April 2024...ANGLE is presenting a poster entitled the 'Development and analytical validation of a novel assay for HER2 assessment on circulating tumor cells harvested using the Parsortix® system and incorporating BioView imaging technologies'."

"ANGLE plc...is pleased to announce its participation at the 14th European Breast Cancer Conference (EBCC) being held in Milan, Italy on 20 to 22 March 2024...ANGLE presenting two posters highlighting the utility of the Company's new Portrait+ CTC Staining Kit and Portrait HER2 assay"

The commercially available Oncolipsy PD-L1 kit can be used for the quantification of PD-L1 transcripts in CTCs. Expression of PD-L1 in size-based enriched CTCs can predict response to PD-1/PD-L1 blockade therapy.

The assay enables the identification of both HER2 protein and gene copy information from each target cell with minimal cell loss, with the potential for minimally invasive patient monitoring during treatment and better classification of patients who may qualify and benefit from HER2-targeted therapies. An added value of the assay is the practicality of utilizing preserved blood samples, allowing streamline batch shipping of clinical samples.

Cisplatin-induced cell damage has been shown to activate the SDF-1/CXCR4 axis in preclinical models of NSCLC, resulting in the recruitment of a cell subset co-expressing the stemness marker CD133 and CXCR4 (SDF-1 receptor) at distant sites... Out of the 61 enrolled patients, 34 had available CTC data for analysis. In this population, DCR was 64.7%, and the ORR 29.4%. Surgery was performed in 14 pts (41.2%).

HER2+ CTCs were also detected in tissue HER2- patients, indicating further investigations are warranted into the clinical significance of HER2+ CTCs. High CTC counts were associated with an increase in PLR, NLR and PAI-1 levels indicating that high CTC trafficking in MBC is associated with an altered inflammatory response which may aid in metastatic dissemination.

Our results show that the PR1 system can successfully capture CTCs from the blood of patients with resectable LC. Monitoring CTC counts post LC surgery may have prognostic relevance and could have an application in the clinical setting, but future research is required.

Successful xenografting of CTCs from a MBC patient revealed their primary localization in the head and trunk regions of zebrafish embryos. DanioCTC represents a major step forward in endeavors to study the dissemination of individual and rare patient-derived CTCs, thereby enhancing our understanding of metastatic breast cancer biology and facilitating the development of targeted interventions in MBC.

We report that with the use of CTCID markers, single and clusters CTCs can be isolated from ovarian cancer patients with prognostic significance. CTCs isolated from the ovarian vein during surgery are indicative of precursor oligoclonal metastasizing HGSC. Actionable HGSC mutations were found in ctDNA, and may have clinical utility in predicting residual disease, monitoring treatment response, and prognosis in the adjuvant setting.

CTCs were detected across all assessed time points. Regular and dynamic liquid biopsies are essential to assess the clinical relevance of CTCs across the subtypes of EOC. Ongoing follow-up investigation within this patient cohort continues, and further longitudinal sampling is ongoing.

P=N/A; N=60 --> 90 | Trial completion date: Sep 2024 --> Feb 2025 | Trial primary completion date: Sep 2024 --> Feb 2025

No abstracts available

"ANGLE plc...is pleased to announce the publication of a peer-reviewed paper in a special issue of the journal - 'Current Issues in Molecular Biology' Special Issue: Advanced Solutions for Cancer Therapy...This peer-reviewed article brings together supporting evidence for the additional and complementary information that can be obtained from CTCs using the Parsortix® system, demonstrating the value of a dual analyte approach for both CTCs and ctDNA."

Herein, we review the literature in which the microfluidic, label-free Parsortix system is utilised for CTC capture, harvest and analysis, alongside the analysis of ctDNA from a single blood sample. This detailed summary of the literature demonstrates how these two analytes can provide complementary disease information.

Enumerating CTCs throughout treatment in EOC is imperative to assess their clinical significance. Ongoing follow-up and longitudinal sampling of this patient cohort continues.

CTCs isolated from the ovarian vein during surgery are indicative of precursor oligoclonal metastasizing HGSC. Actionable HGSC mutations were found in ctDNA, and may have clinical utility in predicting residual disease, monitoring treatment response, and prognosis in the adjuvant setting.

Dynamic and frequent blood sampling is essential to assess the clinical significance of CTCs across the subtypes of EOC. Ongoing follow-up investigation within this patient cohort continues, and further longitudinal sampling is underway.

"ANGLE plc...is delighted to announce breakthrough results from DNA molecular analysis of cancer patient blood samples that provide a unique insight into the progression of each patient's cancer and how this may be treated...Combined DNA Next Generation Sequencing of CTCs and ctDNA from the same blood sample highlights potential for the Parsortix system to identify key variants (DNA mutations) missed by other approaches to help guide treatment decisions..."

"ANGLE plc...is delighted to announce the publication of breakthrough work by researchers at the University of New Mexico, US, into the role of CTC gene expression in the progression of melanoma brain metastasis. The researchers used the Parsortix system to harvest CTCs for analysis and concluded that '… gene expression in CTCs could be pivotal to prescribing more targeted treatment based on the needs of the patient.'"

"ANGLE plc...is delighted to announce the launch of its Portrait®+ CTC staining kit at the San Antonio Breast Cancer Symposium (SABCS)...This launch follows extensive development, optimisation and validation of the kit to provide advanced immunofluorescent (IF) staining of CTCs harvested from a patient blood sample by the Parsortix technology."

DanioCTC represents a major step forward in the endeavors to study the dissemination of individual and rare patient-derived CTCs, thereby enhancing our understanding of metastatic breast cancer biology and facilitating the development of targeted interventions in MBC. Summary statement: DanioCTC is a novel workflow to inject patient-derived CTCs into zebrafish, enabling studies of the capacity of these rare tumor cells to induce metastases.

P=N/A; Initiation date: Sep 2023 --> Dec 2023

DICCT provides the first-in-human proof-of-principle that digoxin induces a partial dissolution of CTC clusters in patients with metastatic breast cancer at drug levels that are safe and well tolerated. Conceptualization of follow-up trials including Na/K-ATPase inhibitors and patient outcome endpoints are underway.

Our results show that the MeCo score is higher in CTCs compared to PTs and in METs compared to CTCs in early- and late-stage breast cancer, respectively. Therefore, the MeCo score is progressively higher throughout the metastatic cascade in breast cancer. These findings demonstrate that mechanical conditioning is retained during metastatic progression, even as cancer cells transition through the circulation where the initial induction by matrix stiffness is lost.

"ANGLE plc...is pleased to announce the publication of a study using the Parsortix system that sheds new light on the phenotypic characteristics of CTCs in Head and Neck Squamous Cell Carcinoma (HNSCC)...The study, conducted by researchers at the University of Birmingham, UK, demonstrates the feasibility of using mass cytometry, a powerful technique widely used for single cell analysis, for the comprehensive characterisation of CTCs captured by the Parsortix system in HNSCC patients."

P=N/A; Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Sep 2023 --> Sep 2024

"ANGLE plc...announces the publication of a study of disseminated tumour cells (DTCs) in bone marrow from breast cancer patients published in the International Journal of Molecular Sciences...Researchers at the University of Tübingen, Germany, used the Parsortix® system for the isolation and harvest of DTCs from bone marrow samples in 360 breast cancer patients (clinical stages I-IV) and compared results to the standard density centrifugation method for DTC detection."

"ANGLE plc...is pleased to announce its participation at the 6th Advances in Circulating Tumor Cells (ACTC) conference held in Greece from 20-23 September 2023...This included the presentation of nine posters showcasing the Parsortix® system in six cancer types across eight independent study centres."

Our advanced method further presents options for 3D DTC cultures, enabling the individualized testing of targeted therapies for BC patients. In conclusion, we present a novel approach for DTC enrichment, with possibilities for future clinical implications.

However, mesenchymal CTCs and the Parsortix® PC1 system show promise as alternative detection methods. This chapter offers a comprehensive review of clinical studies on CTCs in breast cancer, emphasizing their prognostic and predictive value in different stages of the disease and provides insights into potential future directions in CTC research.

We demonstrate mass cytometry allows high-plex proteomic characterisation of CTCs at single-cell resolution and identify common CTC sub-groups with potential for novel biomarker development and immune checkpoint inhibitor treatment stratification.

P=N/A; N=100 --> 9 | Trial completion date: Jul 2025 --> Aug 2023 | Recruiting --> Terminated | Trial primary completion date: Dec 2023 --> Aug 2023; Futility (slow enrollment)

Average harvest rates using ~20 fixed SKBR3 cells spiked into HV and MBC patient blood samples were 75.0% ± 16.1% (%CV = 22.3%) and 68.4% ± 14.3% (%CV = 21.1%), respectively. These evaluations demonstrate the Parsortix PC1 system linearly and reproducibly harvests tumor cells from blood over a range of 1 to ~100 cells.

P=N/A; N=27; Not yet recruiting; Sponsor:Institut Claudius Regaud