Isolation of Circulating Tumor Cells with TellDx Platform Reveals Potential Mechanism of Resistance to Immune Checkpoint Blockade in Melanoma
--Interrogation of circulating tumor cells (CTCs) shows downregulation of KEAP1 gene promotes resistance to immune checkpoint blockade in melanoma--
--Study provides valuable insights into the power of understanding the biology of
--Study published in NPJ Precision Oncology--
BEVERLY, Mass., March 16, 2023 (GLOBE NEWSWIRE) -- TellBio, Inc., a development stage biotechnology company focused on revolutionizing the detection of cancer through its unique and proprietary circulating tumor cell (CTC) technology, the TellDx CTC System, announces publication of data from the scientific founders that reveal downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade (ICB). The paper, titled “Downregulation of KEAP1 in melanoma promotes resistance to immune checkpoint blockade,” was published on March 02, 2023, in NPJ Precision Oncology (DOI 10.1038/s41698-023-00362-3).
While ICB has significantly improved clinical outcomes in melanoma, a subset of patients do not respond or develop resistance over time. Identifying biomarkers that predict patients who are likely to be resistant to ICB therapy could help deliver personalized and cost-effective therapies to patients. Enrichment of whole CTCs from patient blood samples, via the TellDx platform, and subsequent single cell RNA sequencing (scRNA-seq) may provide a non-invasive strategy to elucidate therapeutic response and resistance to ICB and other chemotherapeutic agents.
“TellBio is focused on the early detection, monitoring and treatment of cancer metastasis,” said Pritesh J. Gandhi, PharmD, CEO, TellBio. “These exciting data demonstrate that isolation of CTCs from melaoma patients with the TellDx platform and subsequent single cell RNA sequencing can reveal pathways of response and resistance to ICB. Proactive monitoring of CTCs while receiving ICB may be able to individualize treatment to ensure optimal outcomes”.
In this paper, authors including TellBio’s scientific founders, Drs. Mehmet Toner, Shyamala Maheswaran, and Daniel A. Haber of The Massachusetts General Hospital Center for Cancer Research, leveraged the TellDx platform to enrich untagged intact melanoma CTCs that enable high quality scRNA-seq. CTCs were isolated from patients with metastatic melanoma, prior to or within eight weeks of initiating ICB. A total of 47 CTCs were confirmed by expression of melanoma lineage markers. Comparing single CTCs from patients who achieved a complete response (CR) to those with progressive disease (PD), the investigators found expression of the antigen presentation gene HLA-A is substantially decreased in a subset of CTCs from patients with progressive disease.
Specifically, they noted that KEAP1 expression was elevated in CTCs from CR patients and undetectable in all but one CTC from patients who experienced disease progression. Loss of KEAP1 expression, which is associated with upregulation of NRF2 signaling within individual melanoma CTCs, contributed to poor response to ICB therapy. Notably, cytotoxic CD8 T cells, regulatory T cells, and activated natural killer cell populations are significantly decreased in tumors with low expression of KEAP1.
“The discovery of the role of KEAP1 in melanoma resistance to immune checkpoint blockade therapy demonstrates that transcriptomic characterization of CTCs can detect mechanisms of sensitivity and resistance,” said Shyamala Maheswaran, PhD, Professor, Surgery, Harvard Medical School, and Molecular Biologist, Surgery, Massachusetts General Hospital.
Overall, these data provide valuable insights into the mechanisms behind melanoma resistance to immune checkpoint blockade therapy and highlight the potential of monitoring CTCs to improve outcomes of patients with cancer. An integrated approach to understand pathways regulating immune responses to guide rational therapy selection will maximize efficacy and minimize toxicity for patients with cancer.
TellDx, the already fully functional diagnostic solution, detects and isolates live CTCs from patient liquid biopsies. The platform has been developed and optimized following a decade of research and development. TellDx offers a unique opportunity to isolate CTCs via its microfluidic diagnostic platform to advance translational and clinical efforts and optimize the lives of patients with cancer. The foundation of the Company’s approach, detection of and targeting CTCs, is based on academic and clinical research generated by The Massachusetts General Hospital and Harvard Medical School.
Company: Annie Partisano | [email protected]
For inquiries about deploying TellDx: Contact [email protected] or visit tellbio.com