Dr. Cha-Mei Tang - Pioneering Liquid Biopsy Innovator
Dr. Tang, could you please provide a brief introduction to yourself for our audience? Additionally, share your entrepreneurship journey?
I received my Bachelor, Master, and Sc.D. degrees from the Electrical Engineering and Computer Science Department of Massachusetts Institute of Technology (M.I.T.). After graduation, I involved myself in research on relativistic electron beams and free electron lasers for about 18 years.
Since from my early days, I have been curious about all aspects of science, life, business and even politics. I decided to start a company called Creatv MicroTech, initially focused on developing techniques to make high aspect ratio structures to improve x-ray imaging. We are still involved in various types of microfabrication research. Sometime after that, I decided to expand into biological applications. I started focusing on research and scientific developments, primarily funded by research grants, but not addressing commercialization.
In 2010, we started developing microfabricated filters, called CellSieveTM, for the purpose of collecting circulating tumor cells (CTCs) from blood of cancer patients. Thus, we started our journey of saving and improving people’s lives by LifeTracDx® blood test.
What contributed to the success of your company?
The success of the company rests with the result of the LifeTracDx® blood test, which is used for cancer screening and cancer diagnostics and is applicable to all solid tumors. Even though I always work closely with my scientists, the success should primarily be attributed to my employees: Platte (Pete) Amstutz, III and Olga Makarova for developing the CellSieveTM microfilter technology, and Daniel L. Adams for identifying and analyzing a biomarker in the blood of cancer patients ignored by others.
Could you elaborate on the role of microfabrication for your product?
Starting in the 2000s, there was a lot of interest in CTCs, which are found in the blood of cancer patients. CellSearch is an instrument that received three FDA approvals to collect CTCs from blood of breast, prostate, and colorectal cancer patients. Many academic groups and companies were also developing technologies to capture CTCs. The development of CellSieveTM microfilters manufacturing was accomplished by 2012.
The CellSieveTM microfilters are 9 mm in diameter and contain 180,000, 7 micron diameter pores. The filters are only 10 microns thick, but very strong. An important feature of the CellSieveTM microfilters is the very low autofluorescence of the filter material, so the imaged cells are very high quality.
We process 7.5 milliliters of whole blood diluted by 7.5 milliliters of fixation buffer for a total of 15 milliliters, which passes through the filter under very low pressure in just three minutes. The process removes all red blood cells and 99.99% of white blood cells. Cells larger than 10 microns are captured on top of the filter, and then the cells are stained with biomarkers of interest, conjugated to fluorescent dyes. The low autofluorescence of the CellSieveTM microfilter enables us to see high quality images of the captured cells.
Please elaborate on the biomarker discovered by Daniel Adams.
When we processed the first cancer patient sample, we captured CTCs, and a lot of large, strange looking cells. However, we could not find any journal publication describing those cells analyzed with fluorescent markers from blood of cancer patients or describing their clinical applications. Adams performed accurate analysis of those strange cells and showed that they are not CTCs, but they express macrophage markers. We confirmed that those cells do exist by talking to CellSearch scientists, who said that they saw those cells on their system, but they are not CTCs, so they did not report them.
We called those cells Cancer-Associated Macrophage-like Cells (CAMLs) and published them in The Proceedings of the National Academy of Sciences (PNAS) in 2014. CAMLs are 25-300 microns in size. They are polynucleated due to the tumor cells they engulfed. The figure of cells shows some examples of the CAMLs. When they are small, they are round or oval shaped. They often grow into large rod-shaped cells. They can grow one tail, and the tail can become very long. Often, they have two tails on opposite sides of the cells. We have processed blood from more than 20 different types of solid tumors and found CAMLs in the blood of all those solid tumor types. The general morphologies of the CAMLs are the same, independent of the type of cancer. We even find CAMLs in stage 1 of all types of solid tumors. However, we do not see CAMLs in healthy individuals.
What are the applications of your blood test?
We call our blood test LifeTracDx® liquid biopsy. It has a wide spectrum of applications both for cancer screening and cancer diagnostics. Details can be found on our website: https://creatvbio.com.
LifeTracDx® liquid biopsy is applicable to all three components of cancer screening: i) detection of cancer in all stages in multiple organs in people who did not previously have cancer, ii) detection of cancer recurrence of cancer patients in remission, and iii) detection of minimal residual disease when terminating treatment. Imaging by x-ray or MRI can be used to detect cancer recurrence, but that requires the tumor to grow bigger in the image. LifeTracDx® can detect cancer recurrence earlier than imaging. For most common solid tumors, CAMLs show up in Stage I on average 80% of the time. This is better than most other cancer screening blood tests currently available.
LifeTracDx® liquid biopsy is also applicable to a broad spectrum of cancer diagnostics useful for oncologists treating cancer patients.
- LifeTracDx® can determine if the patient is responding to a new therapy just 30 days after the first dose. So, patients will not be wasting time receiving ineffective treatment or waiting for imaging to show the tumor grew bigger.
- Many features of CAMLs and CTCs captured on the filter provide useful information about the aggressiveness of the cancer. An example of a CAML that indicates aggressiveness of the cancer is the size of the CAML. Patients with any CAML larger than 50 microns have poor prognosis. The larger the CAML, the worse the patient’s prognosis.
- Many FDA approved therapies, and those in development and in clinical trials target specific markers on the tumor cells. If the tumor expresses these specific markers, then the patient will benefit from these drugs. The test to determine if the patient’s cancer expresses the drug target is called companion diagnostics. Many companion diagnostics require tumor tissue. The cost of acquiring tumor tissue for many cancers can be expensive and difficult. LifeTracDx® can provide companion diagnostics by a blood test. We have developed companion diagnostics for more than 30 types of cancer drugs. For example, we have extensive data to support immunotherapy companion diagnostics by our blood test.
- LifeTracDx® can also provide a continuous monitoring of the patient’s treatment response, providing information not readily available by imaging.
CAMLs are polynucleated cells containing a lot of unfragmented tumor DNA, having a much higher quality than short fragments of circulating tumor DNA. CAML’s DNA is ideal for analysis of mutations, methylations, amplification, and deletions.
Company Name : Creatv MicroTech, Inc
Website : www.creatvmicrotech.com
Cha-Mei Tang, Sc.D. – Founder, President, and CEO
Daniel Adams – Director of clinical R&D
Pete Amstutz – CFO & Director of Business Development
CAMLs are polynucleated giant cells found in the blood of cancer patients. Even though every CAML has a different morphology, CAMLs have a few common features. When they are small, they have round or oval shapes. When they get bigger, they can become rod shaped, and can grow one tail or two tails on opposite sides of the cell. The arrow points to a white blood cell (WBC).
The LifeTracDx® liquid biopsy is also applicable for drug development, enabling drug companies to quickly know the effectiveness of their drug.
Looking ahead, how do you envision growing the Creatv Bio Division of Creatv MicroTech in the near term and in the long run?
It is sad to say that ~40% of Americans will develop cancer in their lifetime. In the United States, cancer is the second leading cause of death. The market size for cancer screening and diagnostics is very large. For example, the valuation of Exact Science, the company that offers Cologuard, is about $16 billion. Creatv Bio has the potential to get an even higher valuation.
Commercialization has been a long road. Because our biomarker is so unique, we wanted others to be confident in our science. We have participated in over 20 clinical studies and trials, each lasting about three years, to gather progression free survival and overall survival data for a 24-month period.
Creatv Bio will start by transitioning from a research focused company to offering commercial services to oncologists, patients, and drug companies. We are opening a CLIA lab in 2023. The CLIA lab will enable processing of patient samples for all the different applications described earlier. We are happy to answer any questions by phone or email. In the future, we will also need to raise venture capital to grow the company faster.
As the field of human and health sciences continues to evolve through research, what significant changes do you anticipate, and how is your company preparing for them?
We are the only company in the world that has developed extensive cancer screening and diagnostic tests created from a database built on CAMLs. In the last couple of years, others have begun to publish their findings of CAML cells in the blood of cancer patients even though most publications give those cells different names. Still, these publications are independent validations of our work. In addition, the National Institute of Health (NIH) put out a solicitation to study those cells, and they call them Tumor Macrophage Hybrid Cells (TMHCs).
Could you shed light on the impact you will have on the healthcare industry?
We believe our LifeTracDx® blood test will have a pronounced positive impact on saving and improving people’s lives worldwide.
“To provide innovative blood tests and biomarkers to enable the selection of the best treatment for cancer patients and monitor treatment response”
“Our LifeTracDx® blood test will have a pronounced positive impact on saving and improving people’s lives worldwide”