Single Cell PathologyTMVisualizing cancer spread
Detecting all types of circulating tumor cells
Recently, it became clear that cells from sprouting cancer blood vessels shed into the circulation in significant numbers2. Cells from sprouting cancer blood vessels are “tumor derived endothelial cells”. They are extremely difficult to detect because they behave very similarly to healthy blood cells. Existing circulating tumor cell tests detect only cells originating from actual cancers tissue. Cancer tissue cells are “epithelial cancer cells” and are easy to distinguish from blood cells.
Our patents cover technologies to expose and analyze both types of cells as well as all other circulating tumor cells at the single cell level3,4,5,6.
How it worksFinding what matters
Removing all healthy cells, exposing cancer cells
XZELL developed and patented four modules to isolate and visualize circulating tumor cells3,4,5
- Proprietary cell lysis for removal of red blood cells
- hMXTM magnetic cell separation for removal of white blood cells
- CryoimmunostainingTM for highly multiplexed staining of cancer cells on standard laboratory slides
- Semi-automated microscopic analysis for identification of cancer cells on slides
This process applies the massive body of knowledge of evidence based cancer diagnostics to circulating tumor cells at the single cell level. Well-described hallmarks of cancer can be re-discovered in isolated circulating cancer cells and cell clumps, including aneuploidy, polyploidy, the expression of stem cell markers, mesenchymal makers, epithelial markers, cell proliferation markers, apoptotic markers and more, enabling diagnostics based on solid visual evidence.
Clinical evidenceA proven technique
Unravelling cell-based cancer biomarkers
Clinical studies for prostate cancer were performed at Siriraj Hospital, Bangkok, Thailand, IRB approval no. SI402/2015.
December 2015 – March 2016
Setup: Blood samples from 120 patients with PSA >4ng/ml receiving prostate biopsy were examined for cells associated with positive biopsies.
Results: Tumor derived endothelial cells but not epithelial circulating tumor cells are strongly associated with positive biopsies.
August 2016 – December 2016
Setup: Cells isolated from blood samples of 60 patients with PSA >4ng/ml and scheduled for prostate biopsy were examined for tumor derived endothelial markers, mesenchymal, epithelial and cell proliferation markers as well as nuclear morphology. Analysis of blood samples was performed blinded against biopsy results. In addition, 40 healthy donors were screened for cancer cells.
Results: 86% sensitivity and 70% specificity when compared to biopsy results. 100% specificity in the group of healthy controls.
Ongoing since March 2017
Setup: Blood samples from 1000 patients with elevated PSA tests are examined for tumor derived endothelial cells, mesenchymal, epithelial and cell proliferation markers. Patients positive for cancer cells but with negative biopsy receive prostate MRI scans and fusion biopsy as indicated. Patients negative for cancer cells receive prostate biopsy as planned (negative blood tests do not affect physician’s decision to biopsy).
Study endpoints: Rate of false negative biopsies, rate of false negative blood tests. Overall sensitivity of biopsy vs. blood test.
1Chaffer & Weinberg (2011). A perspective on cancer cell metastasis. Science, 331(6024), 1559–1564. https://doi.org/10.1126/science.1203543
2Cima et al. (2016). Tumor-derived circulating endothelial cell clusters in colorectal cancer. Science Translational Medicine, 8(345), 345ra89.
3Bhakdi & Malasit. (2011). High gradient magnetic separation of biological material. EP 2 190 585 B1 and depending patents
4Bhakdi (2017). Compositions and methods for identifying rare cells. PCT/US17/20905
5Bhakdi et al. (2010). Optimized high gradient magnetic separation for isolation of Plasmodium-infected red blood cells. Malaria Journal, 9, 38. https://doi.org/10.1186/1475-2875-9-38
6Waseem et al. (2016). Buffer-Optimized High Gradient Magnetic Separation : Target Cell Capture Efficiency is Predicted by Linear Bead-Capture Theory. Journal of Magnetics, 21(1), 125–132.
7 AUA White Paper on THE PREVENTION AND TREATMENT OF THE MORE COMMON COMPLICATIONS RELATED TO PROSTATE BIOPSY UPDATE. The American Urological Association, 2016
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