• Single-cell proteomics can elucidate kinase activity in prostate cancer models

  • Kinase activity in bone metastases and epithelial circulating tumor cells is elevated

BEVERLY, Mass., January 20, 2022 (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, TellDx, and treatment through its complementary therapeutics platform, TellRx, announces publication of data from the scientific founders that provide insights into mechanisms of PI3K/mTOR signaling in preclinical models of prostate cancer. The results were published online yesterday in Cancer Research (DOI 10.1158/0008-5472.CAN-21-2609).

Circulating tumor cells (CTC) isolation is an emerging minimally invasive liquid biopsy approach that provides the basis for a multitude of downstream studies including genomic, transcriptomic, and proteomic analyses. This less invasive approach of isolating viable and intact CTCs with the TellDx platform and subsequent single-cell analyses have been applied to elucidate dynamic adaptations of metastatic cancer cells.

“Patients with advanced solid tumors have variable response to therapy because of differences in biology of primary and metastatic tumor sites. Isolation of the spectrum of CTCs with TellDx and subsequent single-cell proteomic analyses could shed light into mechanisms of drug sensitivity and inform delivery of tailored therapies to potentially optimize patient outcomes,” said Pritesh J. Gandhi, PharmD, CEO, TellBio. 

Cancer progression and selection pressures due to cancer pharmacotherapy result in evolution of the cancer microenvironment. Single-cell proteomics provides critical insights into inter- and intra-tumor heterogeneity and mechanisms of differential therapeutic response across the primary tumor, CTCs, and distal tumor growth.

In this paper, the authors, including TellBio scientific founders, Drs David Ting, Daniel A. Haber, Mehmet Toner, and Shyamala Maheswaran of Massachusetts General Hospital Center for Cancer Research, describe, for the first-time, inter- and intra-tumoral differences in kinase activity (PI3K/mTOR) in mouse models of prostate cancer. Single cell proteomics to assess the differences in PI3K/mTOR signaling across different tumor deposits/metastatic sites and CTC populations was employed using enriched CTCs isolated via the TellDx platform.

Single cell cytometry focused on the proteome demonstrated that PI3K/mTOR signaling differed across tumor sites and lineage of tumor cells explaining the heterogenous response to kinase therapy. Specifically, in prostate cancer models, PI3K/mTOR signaling activity was enhanced in bone metastases compared to lung and liver metastases suggesting that the tumor microenvironment in different distal sites may modulate PI3K/mTOR activity. Furthermore, the authors noted EpCAMhigh primary tumor cells and CTCs harbored higher PI3K/mTOR activity, and these cells co-existed with EpCAMlow mesenchymal populations with attenuated kinase activity.

“The differences that kinase activity in various tumor compartments and across cell states has on the heterogeneous response to targeted therapies has been underappreciated until now. These data are an important step in better understanding metastatic disease and our potential approach to treatment selection,” said Dr.Maheswaran. In the setting of suboptimal response to PI3K/mTOR, combination therapies targeting different tissue compartments and cell populations may result in superior antitumor activity.

About TellBio

The Company is a development stage biotechnology company based in Beverly, Massachusetts, with the goal to revolutionize the detection and treatment of cancer through its unique and proprietary circulating tumor cell (CTC) technology and complementary therapeutics platform, TellDx and TellRx, respectively. TellBio’s vision is to free patients and their families from the tyranny of cancer via both its TellDx and TellRx platforms.

TellDx is a fully functional diagnostics solution aimed at detecting viable CTCs from patient liquid biopsies. TellRx is the therapeutics platform that generates novel anti-cancer medicines by specifically targeting CTCs. The synergy of these platforms offers TellBio a unique opportunity to detect CTCs via a first-in-class, best-in-class microfluidic diagnostic platform and target CTCs with novel therapeutics to optimize outcomes of patients with cancer.

Contacts

Annie Partisano | apartisano@tellbio.com

For inquiries about deploying TellDx:
Contact info@tellbio.com or visit tellbio.com

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