There is a big surge of companies marketing blood tests for cancer screening, making it difficult for customers to decide which test to order. Creatv Bio, a Division of Creatv MicroTech, Inc., provides innovative blood tests to detect and diagnose cancer early when it matters most. Cancer is the second leading cause of death in the United States. Creatv Bio's LifeTracDx® liquid biopsy (blood test) has broad clinical applications ideally suited to serve this market. The clinical capabilities became possible based on a biomarker discovered by Creatv Bio in the blood of patients with solid tumors. This biomarker is found in all solid tumors and in all stages of cancer - even high percentages in stage I of the disease. 

The cancer screening features of this simple blood test include:

* Screen for a single cancer, or a group of cancers, 

* Detect residual disease,

* Detect recurrence earlier than imaging, thereby eliminating the need to wait for the tumor to grow before showing up on imaging.

Creatv Bio's simple blood test can also provide a broad spectrum of cancer diagnostics, including:

* Companion diagnostics to determine if the patient will benefit from a cancer drug instead of requiring a riskier, costlier tissue biopsy. Companion diagnostics are important so patients will not waste time and money on drugs with minimal, if any treatment benefit.

* Patient’s prognosis at any time

* Predict treatment response to new therapy within one treatment cycle,

* Monitor therapy to identify drug resistance rapidly,

* Provide copious, unfragmented tumor DNA for sequencing of mutations. 

Utilizing the clinical applications of these specific tests will reduce morbidity and significantly improve patient outcomes. “We have 25 journal publications and book chapters, and poster presentations at conferences that can be downloaded from our website,” said Dr. Cha-Mei Tang, CEO and Founder of Creatv MicroTech, Inc. She is a brilliant leader who received her BS, MS, and Ph.D. degrees from MIT and is passionate, committed, and focused on Creatv Bio’s objectives to save lives.  

Offering the Best 

According to Cha-Mei, filtration by size is the most suitable method to consistently capture multiple types of tumorassociated cells in the blood, including circulating tumor cells (CTCs) and cancer-associated macrophage-like cells (CAMLs). This is the only platform that has captured and identified CAMLs consistently. “Our CellSieveTM microfilter provides a straightforward assay protocol requiring 7.5 mL of whole blood, diluted by 7.5 mL of prefixation buffer (total 15 mL), and then filtered in only 3 minutes, removing all red blood cells and 99.99% of white blood cells,” she explained. “After staining the captured cells on the filter, the filter is removed and mounted on a glass slide with a cover slip followed by imaging the cells under the microscope.”

The properties of CellSieveTM microfilters are:

* Uniform pore size (7 µm diameter) with 180,000 pores in a 9 mm diameter area.

* 10 µm thick, enabling filtration at low pressure.

* Lies flat on glass slides because of the strong filter material

* Low auto-fluorescent background, enabling images of cell features and facilitating the ability to visualize details of cells and to quantify the staining intensity of markers of interest on the cells, enabling companion diagnostics application.

No other researcher or company has fabricated microfilters with features that match CellSieveTM .

Creatv Bio stands out as an essential liquid biopsy company because of the identification of a novel biomarker. The biomarker is one type of tumor macrophage hybrid cell called Cancer Associated Macrophage-like cells (CAMLs) (Figure 1). This marker, used in LifeTracDx® Liquid Biopsy, was seemingly ignored by everyone – thus, their clinical applications went unnoticed except by Creatv Bio.

“We filed patents for every discovery related to CAMLs - a total of 15 patents, and 12 of them are PCTs that have been filed. For the PCTs, patents were chosen to be filed in many countries outside the US. Many patents have been issued and many are ongoing,” adds Dr. Tang. “Currently, no competitor marketing CAMLs has yet emerged. However, in the past 24 months, we have noticed that many academic and private groups have begun to publish papers describing these tumor macrophage hybrid cells, although calling them different names. This independent validation lends a high degree of credence to our claims for the important role that CAMLs play in the early detection and diagnosis of cancer,” she added.

CAMLs are macrophages that engulf and consume tumor material originating at the tumor site. They are enormous, 25-300 µm in size, and poly-nucleated. Cha-Mei Tang and her team found CAMLs in peripheral blood from >20 different types of solid tumors but not in healthy patient controls. Furthermore, CAMLs are found in all stages of cancer, even in high percentages of patients with stage I disease. Despite their size and familiar presence in the blood of cancer patients, no one studied their biology or clinical applications before Creatv Bio.

Figure 1. Four typical morphologies of CAMLs are: round, with 1 tail, with 2 tails on opposite sides, and rod shape. CAMLs are poly-nucleated. The cytoplasm can express various markers. DAPI (blue), CK8, 18, 19 (green), and CD24 (violet).

Saving Time & Money

Creatv Bio collaborates with researchers and offers services to Pharma and Biotech companies, helping them develop their drugs. The critical factors for drug companies are determining whether their drug is effective in the cancer patients enrolled in their clinical trials, as quickly as possible. These studies are very costly and can take years to complete, so knowing if a drug works is essential in saving time and money.

Using Creatv Bio’s CAML biomarker can help companies select the proper patients for entry into their trials, thus maximizing the chances a drug will work against a particular type of cancer. One drug company enrolled a patient in a trial who met their inclusion/exclusion criteria, but died within a few weeks after being admitted into the trial. Creatv Bio’s assay revealed that this patient had a few abnormally large CAMLs, consistent with published data suggesting poor prognosis. [Tang and Adams, Biomedicines 2022]. This supports Creatv Bio’s suggestion that CAML size should be an absolute inclusion/exclusion criterion for patient selection. 

The ability to provide a prognosis helps understand the cancer treatment response. In addition to CAML size, Creatv Bio has also identified other features of CAMLs that can also provide a prognosis. One published marker in CAMLs that predicts poor prognosis is the presence of micronuclei [Kasabwala et al., Biomedicines 2022]. Other markers are under publication review.

Creatv Bio is currently focused on collaborating with cancer drug companies to understand the effectiveness of their drugs. “Soon, we are planning to open a CLIA-certified lab in New Jersey that will enable us to process patient samples and report the results back to the patient or the physician. The current plan is to recruit customers throughout the US,” remarked Dr. Tang. “It is our eventual goal to commercialize LifeTracDx® worldwide. Initially, we will focus on North America, followed by Europe, Japan and Australia. We also intend to identify strategic partners worldwide.”