Overview

Creatv Bio developed a blood test that isolates virtually all cancer associated cells from 7.5 mL of whole blood by using a specially designed microfilter that removes > 99.9% of red and white blood cells.

The cancer associated cells are collected using the microfilter. Cells are stained for the nucleus and markers of interest, followed by imaging under the microscope.

Before 2014, circulating tumor cells (CTCs) were the only widely recognized cancer associated cells. Creatv Bio's assay captures a variety of cell types. Creatv Bio has systematically identified, categorized, and validated these cells as cancer associated through clinical trials.

Cancer Biomarkers

Several types of cancer associated cells from the tumor site enter the blood stream.

  • Circulating Tumor Cells (CTCs)
  • Epithelial Mesenchymal Transition Cells (EMT CTCs)
  • Tumor-Macrophage Hybrid Cells (TMHCs)
    • Cancer Associated Macrophage-Like Cells (CAMLs)
    • Other subtypes
    • Clusters

Creatv Bio's blood test reports the number of each of these types of cells. For CAMLs, the report also includes the size.

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Circulating Tumor Cells (CTCs)

Pathologically defined CTCs, where CK 8, 18, 19 have a filamentous structure. CTCs do not express CD45.
DAPI (blue), CK 8, 18, 19 (green), and CD45 (violet).
CellSieve™ can capture CTCs in various stages of mitosis.
Apoptotic CTC, where CK 8, 18, 19 (green color) appear as dots.

Tumor Macrophage Hybrid Cells (TMHCs)

TMHCs includes all cells which interact with macrophage and tumor cells. The cancer associated cells found in the blood of cancer patients provides a spectrum of clinical diagnostics, cancer screening and drug development applications.

Diagram illustrating five macrophage-tumor cell fusion types, from partial fusion to CAMLs, with fluorescence microscopy examples at 30–100 µm scale.

Cancer Associated Macrophage-like Cells (CAMLs)

Characteristics of CAMLs:

  • 25-300 µm in size
  • Shapes: round, oval, rod, one tail or two tails on opposite sides
  • Polynucleated – nucleic material can be spread out or concentrated in one cluster
  • Macrophages that have engorged tumor cells containing
  • Tumor proteins - applicable for companion diagnostics and drug development
  • Tumor DNA - applicable for detection of tumor mutations, amplifications, and deletions
  • Found in the blood stream of
    • All types of cancer
    • All stages of disease
  • Not found in healthy individuals
Fluorescence microscopy showing CAMLs varied shapes and sizes relative to platelets, RBCs, WBCs, and CTCs.

CAMLs Provide Broader Diagnostic Utility Than CTCs

CAMLs are found in all stages of cancer and are more prevalent than CTCs.

Circulating Tumor Cells (CTCs): Useful only in late stage of 4 cancers: breast, prostate, colorectal and small cell lung cancers.

CAMLs: Represents substantial improvement over CTCs in 

  • all stages and
  • all cancers
Bar charts comparing CAMLs (84–97% detection across healthy to Stage 4) vs. CTCs (11–35% detection), across six cancer types.
Closeup view of the proprietary CellSieve Microfilters

Proprietary CellSieve™ Microfilters

  • 7 µm pore diameter
  • 180,000 pores precisely spaced in a 9 mm diameter area
  • Low autofluorescence background

Assay

  • Filters 7.5 mL of whole blood in 3 minutes
  • Removes all red blood cells
  • Removes > 99.9% white blood cells
  • Stains the cells on the filter for imaging
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