An Anti-cancer Drug in Short Supply Can Now be Made by Microbes

Thanks to a leap forward in synthetic biology, the plant-derived chemotherapy vinblastine has a new source

Saccharomyces cerevisiae, also known as brewer’s yeast, is seen under a microscope. This species is used around the world to make food and beverages. Easily cultured with a well-known genome, the species has also become a favorite of synthetic biologists for making natural products that are difficult to obtain from their native sources. 

Newswise — The supply of a plant-derived anti-cancer drug can finally meet global demand after a team of scientists from Denmark and the U.S. engineered yeast to produce the precursor molecules, which could previously only be obtained in trace concentrations in the native plant. A study describing the breakthrough was published today in Nature. 

“The yeast platform we developed will allow environmentally friendly and affordable production of vinblastine and the more than 3,000 other molecules that are in this family of natural products,” said project co-leader Jay Keasling, a senior faculty scientist at Lawrence Berkeley National Laboratory and scientific director at the Novo Nordisk Foundation Center for Biosustainability (DTU Biosustain). “In addition to vinblastine, this platform will enable production of anti-addiction and anti-malarial therapies as well as treatments for many other diseases.” Keasling is a biochemical engineer who helped launch the now-booming field of synthetic biology when his team successfully transferred the genetic pathway to produce an antimalarial drug, artemisinin, from an herb called sweet wormwood to the laboratory workhorse microbe, E. coli. He is also a professor of Chemical & Biomolecular Engineering at UC Berkeley. 

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Therapeutic viruses help turbocharge the immune system against cancer

The illustration shows a cancer cell (center) surrounded by immune T-cells augmented with an oncolytic (cancer-fighting) virus. A new study describes how a combination of immunotherapy and virotherapy, using myxoma virus, provides new hope for patients with treatment resistant cancers.

By Richard Harth

The immune system has evolved to safeguard the body from a wildly diverse range of potential threats. Among these are bacterial diseases, including plague, cholera, diphtheria and Lyme disease, and viral contagions such as influenza, Ebola virus and SARS CoV-2.

Despite the impressive power of the immune system’s complex defense network, one type of threat is especially challenging to combat. This arises when the body’s own native cells turn rogue, leading to the phenomenon of cancer. Although the immune system often engages to try to rid the body of malignant cells, its efforts are frequently thwarted as the disease progresses unchecked.The illustration shows a cancer cell (center) surrounded by immune T-cells augmented with an oncolytic (cancer-fighting) virus. A new study describes how a combination of immunotherapy and virotherapy, using myxoma virus, provides new hope for patients with treatment resistant cancers. 

In new research appearing in the journal Cancer Cell, corresponding authors Grant McFadden, Masmudur Rahman and their colleagues propose a new line of attack that shows promise for treatment-resistant cancers.

The approach involves a combination of two methods that have each shown considerable success against some cancers. The study describes how oncolytic virotherapy, a technique using cancer-fighting viruses, can act in concert with existing immunotherapy techniques, boosting the immune capacity to effectively target and destroy cancer cells. 

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Imperial startup GlioQuell has the power to shut down cancer cells

Mitochondria membranes could unlock new cancer treatments

By Ian Mundell

A new company using research from the Department of Brain Sciences will look for drugs to treat brain cancers and diseases of old age.

Cancer cells grow at an extraordinary rate inside the body. To do this, they need energy, which is provided by mitochondria, the powerhouses of the cell. Dr Kambiz Alavian in the Department of Brain Sciences has been looking for ways to turn off cancer cells’ power supply. He has now co-founded a company, GlioQuell, to accelerate the development of a new kind of cancer treatment.

“We think we have a new way of looking at the mitochondria of cancer cells, and of treating cancer, based on reducing the efficiency of these beasts inside the cells,” he says

All cells in the human body contain mitochondria, structures that produce energy and biomolecules for whatever activity the cells need to carry out. Looking closely at the cells involved in glioblastoma, one of the most aggressive and deadliest forms of cancer, revealed that their mitochondria are extraordinarily efficient.

“There is almost no cell that I have seen that is as efficient as these particular cells, in terms of utilising their resources for growth,” says Dr Alavian. “They resemble mini-embryos, growing very quickly inside the brain.”

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Proton beam therapy for bone cancer spares surrounding tissue

By Rhoda Madson,  Mayo Clinic

July is Sarcoma Awareness Month, bringing attention to a group of cancers that begin in the bones or soft tissues of the body. There are more than 70 types of sarcoma, including bone cancer. Treatments for bone cancer include surgery, chemotherapy, radiation, or proton beam therapy that targets the cancer.

Proton beam therapy is a type of radiation therapy that is more precise than traditional X-ray treatment that delivers radiation to everything in its path. Proton beam therapy uses charged particles in an atom—protons—that release their energy within the tumor. Because proton beams can be much more finely controlled, specialists can use proton beam therapy to safely deliver higher doses of radiation to tumors. This is especially important for bone cancers.

“Bone tumors need much higher doses of radiation than a sarcoma that arises purely in the muscle, which we call a soft tissue sarcoma,” says Safia Ahmed, M.D., a radiation oncologist at Mayo Clinic. “These high doses of radiation often exceed what the normal tissues around the area can tolerate. Proton therapy allows us to give this high dose of radiation while protecting the normal tissues.”

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A Sensor Sniffs for Cancer, Using Artificial Intelligence

Biomedical engineer Daniel Heller leads the Cancer Nanomedicine Laboratory at MSK.

Researchers at Memorial Sloan Kettering Cancer Center (MSK) have developed a sensor that can be trained to sniff for cancer, with the help of artificial intelligence.

Although the training doesn’t work the same way one trains a police dog to sniff for explosives or drugs, the sensor has some similarity to how the nose works. The nose can detect more than a trillion different scents, even though it has just a few hundred types of olfactory receptors. The pattern of which odor molecules bind to which receptors creates a kind of molecular signature that the brain uses to recognize a scent.

Like the nose, the cancer detection technology uses an array of multiple sensors to detect a molecular signature of the disease. Instead of the signals going to the brain, they are interpreted by machine learning — a type of computer artificial intelligence.

MSK researchers led by Kravis WiSE Postdoctoral Fellow Mijin Kim and biomedical engineer Daniel Heller, head of the Cancer Nanomedicine Laboratory at MSK, built the technology using an array of sensors composed of carbon nanotubes. Carbon nanotubes are tiny tubes, nearly 100,000 times smaller than the width of a human hair. They are fluorescent, and the light they give off is very sensitive to minute interactions with molecules in their environment.

Each nanotube sensor can detect many different molecules in a blood sample. By combining the many responses of the sensors, the technology creates a unique fluorescent pattern. The pattern can then be recognized by a machine-learning algorithm that has been trained to identify the difference between a cancer fingerprint and a normal one.

In experiments conducted on blood samples obtained from patients with ovarian cancer, the researchers found that their nanosensor detected ovarian cancer more accurately than currently available biomarker tests. (A biomarker is a particular chemical produced by tumors and spread through the blood circulation that indicates the presence of disease. In this case, the biomarker tests were ones for the ovarian cancer-related proteins CA125, HE4, and YKL40.)

The hope for patients is that researchers will develop the technology further so that it can eventually be used in the clinic to rapidly screen for early-stage ovarian cancer and many other cancers.Molecular Pharmacology ProgramOur research program serves as a conduit for bringing basic science discoveries to preclinical and clinical evaluation.

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New Technology Could Offer 50-fold Boost For Testing Cancer Therapies

By Dr Sheena Meredith

A new technology platform developed by researchers in Scotland could boost the number of tests that can be performed on a solid tumour sample by up to 50 times. The technique could enable large-scale testing of immunotherapies, and accelerate the development of novel cancer treatments, its developers said.

The team, from the universities of Strathclyde and Glasgow, the Technology and Innovation Centre in Glasgow, and the Cancer Research UK Beatson Institute in Glasgow, explained that while chimeric antigen receptor-T (CAR-T) cell immunotherapies have been “remarkably successful” in the treatment of haematological malignancies, using cellular immunotherapy to treat solid tumours has been more challenging.

Widespread application of CAR-T therapy has been hampered because of high manufacturing costs of CAR-T cell production, which requires an autologous acquisition process from patients. In addition, off-target toxicity can trigger serious or even life-threatening therapy responses.

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Made in Israel: First AI-designed Antibody Could Lead to Eradication of Tumors 

A computer may design the perfect antibody to fight cancer in a breakthrough for medicine. Prof. Yanay Ofran explains why testing it on mice can be misleading, and what limits creativity in biotech companies: ‘They’re searching for a new biology and trying to treat it using old technology. We do the opposite.

In recent weeks certain doctors and patients with terminal cancer in Australia have been participating in a highly important experiment. The doctors are injecting the patients with an antibody that they hope will activate a molecule familiarly known as IL-2, which is naturally produced in the human body and can eradicate tumors.

What makes the experiment unusual is that the antibody they’re injecting wasn’t produced by living tissue, but rather by computers in the laboratory of Biolojic Design in Rehovot. The antibody, known as AU-007, is the first to be designed by computer and reach the stage of clinical trials. It evokes keen hopes because if it works, it paves the way for the development of a new kind of drug based on computational biology and big data.

Like practically every drug that enters clinical trials on humans, Biolojic Design’s antibody was first tested on mice. All evinced positive reactions to the treatment. In the 17-day trial period of the study, the antibody led to the complete elimination of the tumors in ten of 19 mice, and significantly inhibited the development of tumors in the nine other mice.

Prof. Yanay Ofran, founder and CEO of Biolojic Design, is keeping his enthusiasm strictly curbed. “We have a joke we tell at conferences. ‘We have great news for all the mice in the audience. We’ve managed to infect and sicken them with 1001 diseases and cure them.’ The lingua franca of the drug development world, the empiric language it uses, is animal studies. You have to show success with an animal trial or you won’t be able to raise money, the regulator won’t let you test it on people, and doctors won’t refer their patients to the trial.”

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Scientists Develop “Nanomachines” That Can Penetrate and Kill Cancer Cells

A research team from the Korea Institute of Science and Technology has developed ‘nanomachines,’ which use mechanical molecular movements to penetrate and destroy cells. Selective cancer cell penetration is also possible by using a latch molecule released near cancer cells.

Researchers have created ‘nanomachines’ that use mechanical molecular motions to enter and destroy cells.

Cancer is a condition where some of the body’s cells grow out of control and spread to other bodily regions. Cancer cells divide continually, leading them to invade surrounding tissue and form solid tumors. The majority of cancer treatments involve killing the cancer cells.

According to 2020 estimates, 1.8 million new instances of cancer were diagnosed in the US, and 600,000 people passed away from the condition. Breast cancer, lung cancer, prostate cancer, and colon cancer are the most common cancers. The average age of a cancer patient upon diagnosis is 66, and individuals between the ages of 65 and 74 account for 25% of all new cancer diagnoses.

Proteins are involved in every biological process and use the energy in the body to change their structure via mechanical movements. They are referred to as biological ‘nanomachines’ since even minor structural changes in proteins have a substantial impact on biological processes. To implement movement in the cellular environment, researchers have focused on the development of nanomachines that imitate proteins. However, cells use a variety of mechanisms to defend themselves against the effect of these nanomachines. This restricts any relevant mechanical movement of nanomachines that could be used for medical purposes.

The research team headed by Dr. Youngdo Jeong from the Center for Advanced Biomolecular Recognition at the Korea Institute of Science and Technology (KIST) has reported the development of a novel biochemical nanomachine that penetrates the cell membrane and kills the cell via the molecular movements of folding and unfolding in certain cellular environments, such as cancer cells. They collaborated with the teams of Professor Sang Kyu Kwak from the School of Energy and Chemical Engineering and Professor Ja-Hyoung Ryu from the Department of Chemistry at the Ulsan National Institute of Science and Technology (UNIST), and Dr. Chaekyu Kim of Fusion Biotechnology, Inc.

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Nanosensor Platform Could Advance Detection of Ovarian Cancer

Ovarian cancer kills 14,000 women in the United States every year. It’s the fifth leading cause of cancer death among women, and it’s so deadly, in part, because the disease is hard to catch in its early stages. Patients often don’t experience symptoms until the cancer has begun to spread, and there aren’t any reliable screening tests for early detection.

A team of researchers is working to change that. The group includes investigators from Memorial Sloan Kettering Cancer Center, Weill Cornell Medicine, the University of Maryland, the National Institutes of Standards and Technology, and Lehigh University.

Two recent papers describe their advancements toward a new detection method for ovarian cancer. The approach uses machine learning techniques to efficiently analyze spectral signatures of carbon nanotubes to detect biomarkers of the disease and to recognize the cancer itself.

The first paper appeared in Science Advances in November.

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TOPICS:CancerDNAMolecular BiologyPublic HealthYale University

Illustration of human cancer cells.


A team of researchers led by Yale University scientists can now quantify the factors causing changes in the DNA that contribute most to cancer growth in tumors of most major tumor types

In a new paper published in the journal Molecular Biology and Evolution, they say that their new molecular analysis approach clarifies a long-standing debate about how much control humans have over cancer development over time.

Looking at the instances of specific genetic mutations can reveal the extent to which preventable exposures like ultraviolet light caused tumor growth in 24 cancers, said Jeffrey Townsend, Ph.D., the Elihu Professor of Biostatistics in the Department of Biostatistics at Yale School of Public Health (YSPH).

“We can now answer the question — to the best of our knowledge — ‘What is the underlying source of the key mutations that changed those cells to become a cancer instead of remaining normal tissue?’” he said.

Some of the most common cancers in the United States are known to be highly preventable by human decisions. Skin cancers, such as melanoma, emerge in large part because of prolonged exposure to ultraviolet light, and lung cancers can often be traced back to tobacco use. But scientists have long struggled to gauge how much any individual’s tumor developed as a result of preventable actions versus aging or “chance.”

Continue reading… “TOPICS:CancerDNAMolecular BiologyPublic HealthYale University

CAR T Cells “Loaded” with Oncolytic Viruses Boost Attack on Solid Tumors

A new cancer immunotherapy approach devised by Mayo Clinic researchers combines chimeric antigen receptor (CAR) T-cell therapy with a cancer-killing virus. In animal models, the dual therapy, in the form of a virus-loaded CAR T cell, has been shown to target and treat solid cancer tumors more effectively than either the CAR T-cell therapy or the virus alone, or indeed, the CAR T-cell therapy and the virus administered sequentially.

Details about the new approach appeared in Science Translational Medicine, in an article titled, “Oncolytic virus–mediated expansion of dual-specific CAR T cells improves efficacy against solid tumors in mice.” The article indicates that virus-loaded CAR T cells can transfer and release an oncolytic virus in the vicinity of tumor cells, and that tumor cells subsequently become infected, suffer viral replication, and burst open. This sequence of events leads to a potent immune response.

“We show in an immunocompetent mouse model that coadministration of an oncolytic virus (OV) with CAR T cells expands dual-specific (DS) CAR T cells through presentation of viral antigens through their T-cell receptor (TCR),” the article’s authors wrote. “[This approach confers] a potent proliferative advantage, distinct memory phenotypes, and superior efficacy compared to virus alone or to CAR T cells without OV-mediated TCR stimulation.”

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Researchers develop sound-controlled bacteria to fight cancer

by Emily Velasco,  California Institute of Technology

Since its invention, chemotherapy has proven to be a valuable tool in treating cancers of many kinds, but it has a big downside. In addition to killing cancer cells, it can also kill healthy cells like the ones in hair follicles, causing baldness; and those that line the stomach, causing nausea.

Scientists at Caltech may have a better solution: genetically engineered, sound-controlled bacteria that seek and destroy cancer cells. In a new paper appearing in the journal Nature Communications, researchers from the lab of Mikhail Shapiro, professor of chemical engineering and Howard Hughes Medical Institute investigator, show how they have developed a specialized strain of the bacteria Escherichia coli (E. coli) that seeks out and infiltrates cancerous tumors when injected into a patient’s body. Once the bacteria have arrived at their destination, they can be triggered to produce anti-cancer drugs with pulses of ultrasound.

“The goal of this technology is to take advantage of the ability of engineered probiotics to infiltrate tumors, while using ultrasound to activate them to release potent drugs inside the tumor,” Shapiro says.

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