Press Release

BEVERLY, Mass, July 06, 2023 (GLOBE NEWSWIRE) — TellBio, Inc., a development stage biotechnology company focused on revolutionizing detection of cancer through its unique and proprietary circulating tumor cell (CTC) technology, the TellDx System, announces two publications that demonstrate the utility of CTC molecular analyses in patients with prostate cancer or advanced breast cancer. The papers entitled, “DNA hypomethylation silences anti-tumor immune genes in early prostate cancer and circulating tumor cells,” and “Modeling the novel SERD elacestrant in cultured fulvestrant-refractory HR-positive breast circulating tumor cells” were published in Cell (DOI: 10.1016/j.cell.2023.05.028) and Breast Cancer Research and Treatment (DOI: 10.1007/s10549-023-06998-w), respectively.

“These publications continue to highlight the potential utility of the TellDx technology in a spectrum of clinical settings ranging from early localized disease to advanced metastatic disease. Subsequent analysis of CTCs isolated with the TellDx technology can help explain drivers of cancer progression in nascent disease and guide therapeutic selection in refractory settings,” said Pritesh J. Gandhi, PharmD, CEO, TellBio, Inc.

Cancer is characterized by deoxyribonucleic acid (DNA) hypermethylation or hypomethylation resulting in inactivation of tumor suppressor genes. Specific epigenetic modifications impacting the expression of anti-cancer immune regulatory genes have not been elucidated. Prostate cancer generally evolves slowly from an indolent low-grade localized condition to poorly differentiated tumor with high likelihood of aggressive metastatic CTCs associated with poor prognosis. Among patients with localized prostate cancer, less than 15% of the cancers are detectable with short circulating tumor DNA hypermethylation assays. CTCs have substantially larger genomic coverage to study large DNA hypomethylated domains.

In the Cell publication, the authors, including TellBio Scientific Founders, Drs. Mehmet Toner, Shyamala Maheswaran, and Daniel Haber from Massachusetts General Hospital, applied strict criteria, including both transcriptional and DNA copy-number genomic analyses, to identify large DNA domains consistently hypomethylated in prostate CTCs and tumors. Age-matched healthy donors showed minimal signal whereas patients with localized prostate cancer or metastatic prostate cancer revealed a significant DNA hypomethylation signal. Demethylation of core partially methylated regions during early prostate cancer suppressed immune-related genes, whereas core preserved methylation islands spared proliferation genes. Specifically, hypomethylation of the CD1A-IFI16 gene cluster, which plays a pivotal role in immune recognition pathways, correlates with attenuated RNA expression of CD1A-IFI16 resident genes. Silencing of CD1A-IFI16 impairs recruitment of NKT cells and activated CD8+ T cells, thus turning off immune surveillance and enabling tumor growth. These data demonstrate that blood-based CTCs isolated with the TellDx technology can yield novel insights into cancer biology, as well as potentially enable DNA hypomethylation-based early cancer detection.

“CTCs and single cell analyses can be leveraged to serve as unique windows into the biology of cancer progression and metastasis. Furthermore, CTCs may have potential as complementary biomarkers for early detection of clinically significant cancer,” said David Miyamoto, MD, PhD, Assistant Professor of Radiation Oncology, Harvard Medical School, and Investigator, Massachusetts General Hospital Center for Cancer Research.

In a separate publication, CTCs isolated with the TellDx technology from patients with hormone receptor-positive (HR+) breast cancer who were pre-treated with endocrine therapies were expanded both in vitro and ex vivo to evaluate response to elacestrant. Despite advances in targeted therapies, hormone receptor positive (HR+) metastatic breast cancer (MBC) remains a therapeutic challenge and an area of unmet need. Specifically, breast cancers expressing mutations in ESR1 have emerged as an important contributor in developing resistance to hormonal agents. Circulating tumor cells are precursors of metastatic disease and have shown original and acquired mutations consistent with those expected for advanced HR+ breast cancer.

The investigators, including TellBio Scientific Founders, Drs. Mehmet Toner, Daniel Haber, and Shyamala Maheswaran from Massachusetts General Hospital showed sensitivity and prolonged proliferation arrest with elacestrant in CTC lines from patients harboring either wild-type or mutant ESR1 and who previously received fulvestrant. Elacestrant demonstrated efficacy in progression-free survival regardless of prior treatment with fulvestrant or detectable ESR1 mutation.

“These data demonstrate that CTCs can identify acquired resistance and guide rational sequencing of endocrine therapies. Notably, CTCs, as liquid biopsies, can potentially identify effective biology-based therapeutic options for patients with HR+ MBC refractory to contemporary clinical medicines,” said Aditya Bardia, MD, MPH, Associate Professor of Medicine, Harvard Medical School and Director of Breast Cancer Research Program, Massachusetts General Hospital.