Research could lead to similar treatments for other diseases, as well as creating a demand for a new line of oncology tests for clinical labs and pathology groups
Cancer treatment has come a long way in the past decades, and it seems poised to take another leap forward thanks to research being conducted at Rice University in Houston. Molecular scientists there have developed what they call a “molecular jackhammer” that uses special molecules and near-infrared light to attack and kill cancer cells.
The technique has been effective in research settings. Should it be cleared for use in patient care, it could change the way doctors treat cancer patients while giving clinical laboratories a new diagnostic tool that could guide treatment decisions.
The researchers “found that the atoms of a small dye molecule used for medical imaging can vibrate in unison—forming what is known as a plasmon [a quantum of plasma oscillation]—when stimulated by near-infrared light, causing the cell membrane of cancerous cells to rupture,” a Rice University news release noted.
The small dye molecule is called aminocyanine, a type of fluorescent synthetic dye that is already in use in medical imaging.
“These molecules are simple dyes that people have been using for a long time,” said physical chemistry scientist Ciceron Ayala-Orozco, PhD, the researcher who led the study, in the news release. “They’re biocompatible, stable in water, and very good at attaching themselves to the fatty outer lining of cells. But even though they were being used for imaging, people did not know how to activate these as plasmons.”
“The method had a 99% efficiency against lab cultures of human melanoma cells, and half of the mice with melanoma tumors became cancer-free after treatment,” according to the Rice University news release.
“I spent approximately four years working with these ideas on using molecular forces and what is called blue-light activated molecular motors,” Ciceron Ayala-Orozco, PhD (above), told Oncology Times. “At some point, I connected the dots that what I wanted to do is use a simple molecule, not necessarily a motor, that absorbs NIR light in similar ways as plasmonic nanoparticles do and go deeper into the tissue. When activated, we found that the molecules vibrate even faster than our minds can imagine and serve as a force to break the cancer cells apart.” Once approved for use treating cancer patients, clinical laboratories working with oncologists may play a key role in diagnosing candidates for the new treatment. (Photo copyright: Rice University.)
How the Technique Works
Nuclei of the aminocyanine molecules oscillate in sync when exposed to near-infrared radiation and pummel the surface of the cancer cell. These blows are so powerful they rupture the cell’s membrane sufficiently enough to destroy it.
“The speed of this type of therapy can completely kill the cancer much faster than, say, photodynamic therapy,” Ayala-Orozco noted. “The mechanical action through the molecular jackhammer is immediate, within a few minutes.”
One advantage to near-infrared light is that it can infiltrate deeper into the body than visible light and access organs and bones without damaging tissue.
“Near-infrared light can go as deep as 10 centimeters (four inches) into the human body as opposed to only half a centimeter (0.2 inches), the depth of penetration for visible light, which we used to activate the nanodrills,” said James Tour, PhD, T. T. and W. F. Chao Professor of Chemistry, Professor of Materials Science and NanoEngineering at Rice University, in the news release. “It is a huge advance.”
The molecular plasmons identified by the team had a near-symmetrical structure. The plasmons have an arm on one side that does not contribute to the motion, but rather anchors the molecule to the lipid bilayer of the cell membrane. The scientists had to prove that the motion could not be categorized as a form of either photodynamic or photothermal therapy.
“What needs to be highlighted is that we’ve discovered another explanation for how these molecules can work,” Ayala-Orozco said in the Rice news release. “This is the first time a molecular plasmon is utilized in this way to excite the whole molecule and to actually produce mechanical action used to achieve a particular goal—in this case, tearing apart cancer cells’ membrane.
“This study is about a different way to treat cancer using mechanical forces at the molecular scale,” he added.
New Ways to Treat Cancer
The likelihood of cancer cells developing a resistance to these molecular jackhammers is extremely low, which renders them a safer and more cost effective method for inducing cancer cell death.
“The whole difference about this is because it’s a mechanical action, it’s not relying on some chemical effect,” Tour told KOMO News. “It’s highly unlikely that the cell will be able to battle against this. Once it’s cell-associated, the cell is toast once it gets hit by light. Only if a cell could prevent a scalpel from being able to cut it in half, could it prevent this.
“It will kill all sorts of cell types. With our other mechanical action molecules, we’ve demonstrated that they kill bacteria; we’ve demonstrated that they kill fungi. If a person has lost the ability to move a limb, if you can stimulate the muscle with light, that would be quite advantageous. Cancer is just the beginning,” he added.
“From the medical point of view, when this technique is available, it will be beneficial and less expensive than methods such as photothermal therapy, photodynamics, radio-radiation, and chemotherapy,” said Jorge Seminario, PhD, Professor in the Artie McFerrin Department of Chemical Engineering at Texas A&M University in a news release.
“This is one of the very few theoretical-experimental approaches of this nature. Usually, research in the fields related to medicine does not use first principles quantum-chemistry techniques like those used in the present work, despite the strong benefit of knowing what the electrons and nuclei of all atoms are doing in molecules or materials of interest,” Seminario noted.
“It’s really a tremendous advance. What this is going to do is open up a whole new mode of treatment for medicine,” Tour said. “It’s just like when radiation came in [and] when immunotherapy came in. This is a whole new modality. And when a new modality comes in, so much begins to open up.
“Hopefully, this is going to change medicine in a big way,” he added.
More research and clinical studies are needed before this new technology is ready for patient care. Clinical laboratories and anatomic pathology groups will likely be involved identifying patients who would be good candidates for the new treatment. These molecular jackhammers could be a useful tool in the future fight against cancer, which is ranked second (after heart disease) as the most common cause of death in the US.
Immunotherapy device could also enable clinical laboratories to receive in vivo biomarker data wirelessly
Researchers from Rice University in Houston and seven other states in the US are working on a new oncotherapy sense-and-respond implant that could dramatically improve cancer outcomes. Called Targeted Hybrid Oncotherapeutic Regulation (THOR), the technology is intended primarily for the delivery of therapeutic drugs by monitoring specific cancer biomarkers in vivo.
Through a $45 million federal grant from the Advanced Research Projects Agency for Health (ARPA-H), the researchers set out to develop an immunotherapy implantable device that monitors a patient’s cancer and adjusts antibody treatment dosages in real time in response to the biomarkers it measures.
It’s not a far stretch to envision future versions of the THOR platform also being used diagnostically to measure biomarker data and transmit it wirelessly to clinical laboratories and anatomic pathologists.
ARPH-A is a federal funding agency that was established in 2022 to support the development of high-impact research to drive biomedical and health breakthroughs. THOR is the second program to receive funding under its inaugural Open Broad Agency Announcement solicitation for research proposals.
“By integrating a self-regulated circuit, the THOR technology can adjust the dose of immunotherapy reagents based on a patient’s responses,” said Weiyi Peng, MD, PhD (above), Assistant Professor of Biology and Biochemistry at the University of Houston and co-principal investigator on the research, in a UH press release. “With this new feature, THOR is expected to achieve better efficacy and minimize immune-related toxicity. We hope this personalized immunotherapy will revolutionize treatments for patients with peritoneal cancers that affect the liver, lungs, and other organs.” If anatomic pathologists and clinical laboratories could receive biometric data from the THOR device, that would be a boon to cancer diagnostics. (Photo copyright: University of Houston.)
Antibody Therapy on Demand
Omid Veiseh, PhD, Associate Professor of Bioengineering at Rice University and principal investigator on the project, described the THOR device as a “living drug factory” inside the body. The device is a rod-like gadget that contains onboard electronics and a wireless rechargeable battery. It is three inches long and has a miniaturized bioreactor that contains human epithelial cells that have been engineered to produce immune modulating therapies.
“Instead of tethering patients to hospital beds, IV bags, and external monitors, we’ll use a minimally invasive procedure to implant a small device that continuously monitors their cancer and adjusts their immunotherapy dose in real time,” said Veiseh in a Rice University press release. “This kind of ‘closed-loop therapy’ has been used for managing diabetes, where you have a glucose monitor that continuously talks to an insulin pump.
But for cancer immunotherapy, it’s revolutionary.”
The team believes the THOR device will have the ability to monitor biomarkers and produce an antibody on demand that will trigger the immune system to fight cancer locally. They hope the sensor within THOR will be able to monitor biomarkers of toxicity for the purpose of fine-tuning therapies to a patient immediately in response to signals from a tumor.
“Today, cancer is treated a bit like a static disease, which it’s not,” Veiseh said. “Clinicians administer a therapy and then wait four to six weeks to do radiological measurements to see if the therapy is working. You lose quite a lot of time if it’s not the right therapy. The tumor may have evolved into a more aggressive form.”
The THOR device lasts 60 days and can be removed after that time. It is designed to educate the immune system to recognize a cancer and prevent it from recurring. If the cancer is not fully eradicated after the first implantation, the patient can be implanted with THOR again.
Use of AI in THOR Therapy
The researchers plan to spend the next two and a half years building prototypes of the THOR device, testing them in rodents, and refining the list of biomarkers to be utilized in the device. Then, they intend to take an additional year to establish protocols for the US Food and Drug Administration’s (FDA) good manufacturing practices requirements, and to test the final prototype on large animals. The researchers estimate the first human clinical trials for the device will begin in about four years.
“The first clinical trial will focus on refractory recurrent ovarian cancer, and the benefit of that is that we have an ongoing trial for ovarian cancer with our encapsulated cytokine ‘drug factory’ technology,” said Veiseh in the UH press release.
The group is starting with ovarian cancer because research in this area is lacking and it will provide the opportunity for THOR to activate the immune system against ovarian cancer, which is typically challenging to fight with immunotherapy approaches. If successful in ovarian cancer, the researchers hope to test THOR in other cancers that metastasize within the abdomen, such as:
All control and decision-making will initially be performed by a healthcare provider based on signals transmitted by THOR using a computer or smartphone. However, Veiseh sees the device ultimately being powered by artificial intelligence (AI) algorithms that could independently make therapeutic decisions.
“As we treat more and more patients [with THOR], the devices are going to learn what type of biomarker readout better predicts efficacy and toxicity and make adjustments based on that,” he predicted. “Between the information you have from the first patient versus the millionth patient you treat, the algorithm is just going to get better and better.”
Moving Forward
In addition to UH and Rice University, scientists working on the project come from several institutions, including:
More research and clinical trials are needed before THOR can be used in the clinical treatment of cancer patients. If the device reaches the commercialization stage, Veiseh plans to either form a new company or license the technology to an existing company for further development.
“We know that the further we advance it in terms of getting that human data, the more likely it is that this could then be transferred to another entity,” he told Precision Medicine Online.
Pathologists and clinical laboratories will want to monitor the progress of the THOR technology’s ability to sense changes in cancer biomarkers and deliver controlled dosages of antibiotic treatments.
Citizens claiming racial diversity increased by 276% in the 2020 census, leading experts to wonder if racial diversity is increasing or if people are simply electing to identify as such and how this trend will affect healthcare
Once again, we see another unexpected consequence to expanded DNA testing done by consumers for their own interests and needs. As NPR recently reported in “The Census Has Revealed a More Multiracial US. One Reason? Cheaper DNA Tests,” the growing trend of ordering low-cost direct-to-consumer (DTC) genetic testing to identify cultural heritage (where a family came from) and genealogy (to connect with extant family members) has educated healthcare consumers more about their cultural roots.
Such knowledge, NPR speculates, is allowing people to complete their census survey with more accurate “heritage” classifications.
The last US census showed an interesting change compared to previous census surveys. More Americans identified themselves as racially diverse than in previous censuses. Scientists in multiple specialty areas—including demographics, sociology, genetics, and more—are asking why.
According to federal Census Bureau data, in the most recent census, people who identify as more than one race rose by 276%! Scientists are only just beginning to hypothesize the reasons for this increase, but three potential factors, NPR reported, have emerged:
More children are being born to parents who identify with racial groups that are different from one another.
People are reconsidering what they want the government to know about their identities, according to Duke University Press.
The increased incidence of DNA testing for cultural heritage may be an additional factor in the different ways people identified themselves during the census, driving its popularity, NPR noted. More people are purchasing at-home DNA tests to learn where their ancestors lived and came from, and their family’s genealogy.
“Exactly how big of an effect these tests had on census results is difficult to pin down,” NPR reported. “But many researchers agree that as the cost of at-home kits fell in recent years, they have helped shape an increasing share of the country’s ever-changing ideas about the social construct that is race.”
How the Census Alters Government Policy
Pew Research noted that, although only about 16% of Americans have taken an ancestry DNA test, the marketing efforts of “companies such as 23andMe and Ancestry.com, which operates the AncestryDNA service, should not be underestimated,” NPR reported. They have a wide reach, and those efforts could be impacting how people think about race and ethnic identity.
For most of human history, social experience and contemporary family history have been the drivers of how people identified themselves. However, low-cost DTC genetic testing may be changing that.
One concern that sociologists and demographers have about this trend is that the US census is an important tool in policy, civil rights protections, and even how researchers measure things like healthcare access disparities.
“You’re going to have a lot more people who are not part of marginalized groups in terms of their social experiences claiming to be part of marginalized groups. When it comes to understanding discrimination or inequality, we’re going have very inaccurate estimates,” says Wendy Roth, PhD, Associate Professor of Sociology, University of Pennsylvania, told NPR.
They developed the “genetic options” theory, “to account for how genetic ancestry tests influence consumers’ ethnic and racial identities.” They wrote, “The rapid growth of genetic ancestry testing has brought concerns that these tests will transform consumers’ racial and ethnic identities, producing “geneticized” identities determined by genetic knowledge.”
However, a more healthcare-related motivation for taking a DTC DNA test is to learn about one’s potential risks for familial chronic health conditions, such as cancer, heart disease, and diabetes, etc.
“Whether that occurs through your primary care doctor, your large integrated health network, or your payor, I think there will be profound changes in society’s tolerance for using genetics for prevention,” he told GenomeWeb.
Regardless, as Dark Daily reported in 2020, sales of genetic tests from Ancestry and 23andMe show the market is cooling. Thus, with less than 20% of the population having taken DNA tests, and with sales slowing, genetics testing may not affect responses on the next US census, which is scheduled for April 1, 2030.
In the meantime, clinical laboratory managers should recognize how and why more consumers are interested in ordering their own medical laboratory tests and incorporate this trend into their lab’s strategic planning.
Use of synthetic genetics to replicate an infectious disease agent is a scientific accomplishment that many microbiologists and clinical laboratory managers expected would happen
Microbiologists and infectious disease doctors are quite familiar with Escherichia coli (E. coli). The bacterium has caused much human sickness and even death around the globe, and its antibiotic resistant strains are becoming increasingly difficult to eradicate.
Now, scientists in England have created a synthetic “recoded” version of E. coli bacteria that is being used in a positive way—to fight disease. Their discovery is being heralded as an important breakthrough in the quest to custom-alter DNA to create synthetic forms of life that one day could be designed to fight specific infections, create new drugs, or produce tools to diagnose or treat disease.
Scientists worldwide working in the field of synthetic genomics are looking for ways to modify genomes in order to produce new weapons against infection and disease. This research could eventually produce methods for doctors—after diagnosing a patient’s specific strain of bacteria—to then use custom-altered DNA as an effective weapon against that patient’s specific bacterial infection.
This latest milestone is the result of a five-year quest by researchers at the Medical Research Council Laboratory of Molecular Biology (MRC-LMB) in Cambridge, England, to create a man-made version of the intestinal bacteria by redesigning its four-million-base-pair genetic code.
The MRC-LMB lab’s success marks the first time a living
organism has been created with a compressed genetic code.
The researchers published their findings in the journal Nature.
“This is a landmark in the emerging field of synthetic
genomics and finally applies the technology to the laboratory’s workhorse
bacterium,” they wrote. “Synthetic genomics offers a new way of life, while at
the same time moving synthetic biology towards a future in which genomes can be
written to design.”
All known forms of life on Earth contain 64 codons—a specific sequence of three consecutive nucleotides that corresponds with a specific amino acid or stop signal during protein synthesis. Jason Chin, PhD, Program Lead at MRC-LMB, said biologists long have questioned why there are 20 amino acids encoded by 64 codons.
“Is there any function to having more than one codon to encode each amino acid?” Chin asked during an interview with the Cambridge Independent. “What would happen if you made an organism that used a reduced set of codons?”
The MRC-LMB research team took an important step toward
answering that question. Their synthetic E. coli strain, dubbed Syn61,
was recoded through “genome-wide substitution of target codons by defined
synonyms.” To do so, researchers mastered a new piece-by-piece technique that
enabled them to recode 18,214 codons to create an organism with a 61-codon
genome that functions without a previously essential transfer RNA.
“Our synthetic genome implements a defined recoding and refactoring scheme–with simple corrections at just seven positions–to replace every known occurrence of two sense codons and a stop codon in the genome,” lead author Julius Fredens, PhD, a post-doctoral research associate at MRC, and colleagues, wrote in their paper.
Joshua Atkinson, PhD, a postdoctoral research associate at Rice University in Houston, labeled the breakthrough a “tour de force” in the field of synthetic genomics. “This achievement sets a new world record in synthetic genomics by yielding a genome that is four times larger than the pioneering synthesis of the one-million-base-pair Mycoplasma mycoides genome,” he stated in Synthetic Biology.
“Synthetic genomics is enabling the simplification of
recoded organisms; the previous study minimized the total number of genes and
this new study simplified the way those genes are encoded.”
Manmade Bacteria That are Immune to Infections
Researchers from the J.
Craig Venter Institute in Rockville, Maryland, created the first synthetic
genome in 2010. According to an article in Nature,
the Venter Institute successfully synthesized the Mycoplasma mycoides genome
and used it “reboot” a cell from a different species of bacterium.
The MRC-LMB team’s success may prove more significant.
“This new synthetic E. coli should not be able to decode DNA from any other organism and therefore it should not be possible to infect it with a virus,” the MRC-LMB stated in a news release heralding the lab’s breakthrough. “With E. coli already being an important workhorse of biotechnology and biological research, this study is the first time any commonly used model organism has had its genome designed and fully synthesized and this synthetic version could become an important resource for future development of new types of molecules.”
Because the MRC-LMB team was able to remove transfer RNA and
release factors that decode three codons from the E. coli bacteria,
their achievement may be the springboard to designing manmade bacteria that are
immune to infections or could be turned into new drugs.
“This may enable these codons to be cleanly reassigned and
facilitate the incorporation of multiple non-canonical amino acids. This
greatly expands the scope of using non-canonical amino acids as unique tools
for biological research,” the MRC-LMB news release added.
Though synthetic genomics impact on clinical laboratory diagnostics is yet to be known, medical laboratory leaders should be mindful of the potential for rapid innovation in this field as proof-of-concept laboratory innovations are translated into real-world applications.
Genalyte’s cloud-based Maverick Detection System could potentially change how and when doctors order blood draws, altering long-standing clinical laboratory workflows
So far, though, continued efforts to dramatically reduce the amount of blood needed for most typical medical laboratory tests have come up dry. But this has not stopped innovative companies from trying to do so.
One such company is San Diego-based Genalyte. The biomedical diagnostics developer has announced it is readying its new Maverick Detection System (Maverick), which, according to the company’s website, “completes a comprehensive battery of blood tests in the physician’s office with results in 15 minutes.”
According to a news release, “Genalyte is laying the groundwork to move the business of biomedical diagnostics online, with the idea of creating an integrated delivery service for test results that can be generated from a drop of blood.” If successful, Maverick may be poised to disrupt the phlebotomy and clinical laboratory industries in a big way.
Fifteen Minutes from Fingerprick to Clinical Lab Test Results
Maverick, according to its developers, “[will] send digital samples to the cloud for quality review before releasing to the physician and patient. Our central lab handles tests that cannot be completed onsite.
“At the core of our cloud-based, diagnostic laboratory offering is revolutionary technology that uses silicon photonic biosensors to perform multiple tests off a single drop of whole blood in 15 minutes,” notes Genalyte’s website.
In a MedCity News article, Cary Gunn, Genalyte’s founder and CEO, said, “There will always be a need for esoteric testing that needs to be referred to a laboratory. But for the vast majority of routine testing, there’s no reason why that can’t be done in the doctor’s office.”
How Maverick Completes Medical Laboratory Tests in Doctor’s Offices
According to Genalyte’s website, “The Maverick Detection System performs real-time detection of macromolecules in crude samples using biologically functionalized silicon photonic biosensors lithographically printed on disposable silicon chips.”
About the width of a pencil erasure, Maverick biosensor chips “are individually functionalized with unique probe molecules and are individually interrogated, making highly multiplexed analysis possible. As a sample flows over the chip, the probes on the sensors bind with their corresponding ligands. This binding results in a localized change in refractive index on the sensor surface; this change is directly proportional to analyte concentration.”
“The silicon chip itself is watching the chemical reactions take place. Anytime two molecules bind, we can see that happen. So, the technology is capable of almost an infinite number of tests,” Gunn explained in the MedCity News article.
According to the developer, test results are available “in 10-30 minutes depending on the type of assay performed.”
Cary Gunn, PhD, Genalyte’s Founder and Chief Executive Officer, said in a news release that the San Diego-based biomedical diagnostics company wants “to put a rapid and powerful suite of diagnostic tests in every physician’s office.” (Photo copyright: Genalyte.)
Pilot Studies Show Test Feasibility in Doctor’s Offices
The company also announced completion of two pilot studies of the platform’s effectiveness in performing anti-nuclear antibody (ANA) testing. The purpose of study “one” was to “evaluate the feasibility of using this novel instrument to perform ANA 8 tests in the clinic and to compare those results to the same sample tested in Genalyte’s CLIA registered laboratory.” Study “two” focused on “Detection of anti-nuclear antibodies for the diagnosis of connective tissue diseases (CTD).”
The ANA test is often ordered by physicians for diagnosis of CTDs, including:
“We are starting with rheumatology, but I call that our entry point,” Gunn told MedCity News. “Our goal is to decentralize the vast majority of diagnostic testing to be near the patient and near the physician.”
The two studies together involved about 750 patients, who were tested by Genaltye’s Maverick system over four months. Results of their blood tests, via fingerprick in the doctor’s office, were compared to traditional medical laboratory procedures and patient diagnoses.
According to the Genalyte video above, “The Maverick Detection System … directly detects the binding of proteins or antibodies to the sensor in real-time and results are analyzed simultaneously with the accompanying Genalyte software. Almost all of the most time consuming and expensive parts of assay development and sample testing are reduced or eliminated.” Click on the image to view the video. (Caption and video copyright: Genalyte.)
According to the news release and the published clinical abstracts, the researchers concluded that:
• Positive and negative results on whole blood tested on the Maverick system highly correlated with serum tested on previously approved devices;
• Multiplex ANA testing on whole blood in physician offices is feasible;
• Venous draw and fingerstick blood samples highly correlated; and
• Maverick has the propensity to improve patients wait times for diagnosis and to enhance their testing convenience.
“There is extremely high correlation for absolute value between venous blood and fingerstick blood, and between positive and negative results seen with whole blood on the Maverick and serum on the FIDIS Connective 10,” noted study “one” researchers.
“I’m impressed,” Patricia Jones, PhD, former President of the American Association for Clinical Chemistry (AACC), told Bloomberg News. “The game-changing part of this would be being able to do testing and potentially make a diagnosis immediately, instead of having to send out lab tests, wait several days, and then call the patient,” she added.
Can One Drop Do It All? Some Researchers Advise Caution
The controversy surrounding point-of-care fingerprick capillary blood draws performed on in-office automated blood analyzers, versus clinical laboratory venous draws performed on high-volume laboratory systems, is not new. Dark Daily has reported on several blood test studies in the past.
One such study involved bioengineers at Rice University. It concluded that fingerpricked capillary blood may not be accurate or reliable enough for clinical decision-making.
Their study acknowledged the value of such capillary blood testing in remote areas. But it also urged caution about use of measurements from a single drop of fingerprick blood.
“Using both a hematology analyzer and POC hemoglobinometer, we found the variability of blood component measures to be greater for successive drops of fingerprick blood than for multiple drops of venous blood,” the researchers wrote in The American Journal of Clinical Pathology (AJCP).
Research will no doubt continue until a viable, accurate, and affordable blood analyzer system that conducts dozens of clinical laboratory tests based on a few drops of blood comes to market. It’s basically inevitable in today’s world where computers can be built from molecules and miniature medical laboratories can be placed in chips, skin patches, and needles.
Pathologists and clinical laboratory leaders would be well advised to monitor the development of these various new diagnostic technologies. For most of the past decade, there has been a steady parade of companies and research teams announcing new discoveries that could revolutionize clinical diagnostics as performed today. However, few disruptive clinical laboratory tests or analyzers based on these technologies have made it into the clinical marketplace.