Tag: Medicine

A new technology developed at Tel Aviv University makes it possible to destroy cancerous tumors in a targeted manner, via a combination of ultrasound and the injection of nanobubbles into the bloodstream. Unlike invasive treatment methods or the injection of microbubbles into the tumor itself, this latest technology enables the destruction of the tumor in a non-invasive manner.

The study was conducted under the leadership of doctoral student Mike Bismuth from the lab of Dr. Tali Ilovitsh at Tel Aviv University’s Department of Biomedical Engineering, in collaboration with Dr. Dov Hershkovitz of the Department of Pathology. Prof. Agata Exner from Case Western Reserve University in Cleveland also participated in the study. The study was published in the journal Nanoscale.

“Our new technology makes it possible, in a relatively simple way, to inject nanobubbles into the bloodstream, which then congregate around ​​the cancerous tumor. After that, using a low-frequency ultrasound, we explode the nanobubbles, and thereby the tumor.”  Dr. Tali Ilovitsh

Bursting Bubbles – and Tumors

Dr. Tali Ilovitsh: “Our new technology makes it possible, in a relatively simple way, to inject nanobubbles into the bloodstream, which then congregate around ​​the cancerous tumor. After that, using a low-frequency ultrasound, we explode the nanobubbles, and thereby the tumor.”

The researchers explain that today, the prevalent method of cancer treatment is surgical removal of the tumor, in combination with complementary treatments such as chemotherapy and immunotherapy.

The research team

Therapeutic ultrasound to destroy the cancerous tumor is a non-invasive alternative to surgery. This method has both advantages and disadvantages. On the one hand, it allows for localized and focused treatment; the use of high-intensity ultrasound can produce thermal or mechanical effects by delivering powerful acoustic energy to a focal point with high spatial-temporal precision. This method has been used to effectively treat solid tumors deep within in the body. Moreover, it makes it possible to treat patients who are unfit for tumor resection surgery. The disadvantage, however, is that the heat and high intensity of the ultrasound waves may damage the tissues near the tumor.

“The combination of nanobubbles and low frequency ultrasound waves provides a more specific targeting of the area of the tumor and reduces off-target toxicity.” Dr. Tali Ilovitsh

Reducing Off-target Damage

In the current study, Dr. Ilovitsh and her team sought to overcome this problem. In the experiment, which used an animal model, the researchers were able to destroy the tumor by injecting nanobubbles into the bloodstream (as opposed to what has been until now, which is the local injection of microbubbles into the tumor itself), in combination with low-frequency ultrasound waves, with minimal off-target effects.

“The combination of nanobubbles and low frequency ultrasound waves provides a more specific targeting of the area of the tumor, and reduces off-target toxicity,” explains Dr. Ilovitsh.

“Applying the low frequency to the nanobubbles causes their extreme swelling and explosion, even at low pressures. This makes it possible to perform the mechanical destruction of the tumors at low-pressure thresholds.”

“Our method has the advantages of ultrasound, in that it is safe, cost-effective, and clinically available, and in addition, the use of nanobubbles facilitates the targeting of tumors because they can be observed with the help of ultrasound imaging.”

Dr. Ilovitsh adds that the use of low-frequency ultrasound also increases the depth of penetration, minimizes distortion and attenuation, and enlarges the focal point. “This can help in the treatment of tumors that are located deep with the body, and in addition facilitate the treatment of larger tumor volumes. The experiment was conducted in a breast cancer tumor lab model, but it is likely that the treatment will also be effective with other types of tumors, and in the future, also in humans.”

A new study at Tel Aviv University found that aerobic exercise can reduce the risk of metastatic cancer by 72%. According to the researchers, intensity aerobic exercise increases the glucose (sugar) consumption of internal organs, thereby reducing the availability of energy to the tumor.  

The study was led by two researchers from TAU’s Sackler Faculty of Medicine: Prof. Carmit Levy from the Department of Human Molecular Genetics and Biochemistry and Dr. Yftach Gepner from the School of Public Health and the Sylvan Adams Sports Institute. The paper was published in the prestigious journal Cancer Research and chosen for the cover of the November 2022 issue

“If the general message to the public so far has been ‘be active, be healthy’, now we can explain how aerobic activity can maximize the prevention of the most aggressive and metastatic types of cancer.” Prof. Carmit Levy and Dr. Ytach Gepner

Enhanced Rate of Glucose Consumption

Previous studies have demonstrated that physical exercise reduces the risk for some types of cancer by up to 35%. This positive effect resembles the impact of exercise on other conditions, such as heart disease and diabetes.

In this study, Prof. Levy and Dr. Gepner added new insight, showing that high-intensity aerobic exercise, which derives its energy from sugar, can reduce the risk of metastatic cancer by as much as 72%. “If the general message to the public so far has been ‘be active, be healthy’,” they say, “now we can explain how aerobic activity can maximize the prevention of the most aggressive and metastatic types of cancer.”

The study combined lab models trained under a strict exercise regimen, with data from healthy human volunteers examined before and after running. The human data, obtained from an epidemiological study that monitored 3,000 individuals for about 20 years, indicated 72% less metastatic cancer in participants who reported regular aerobic activity at high intensity, compared to those who did not engage in physical exercise.

The animal model exhibited a similar outcome, enabling the researchers to identify its underlying mechanism. They found that aerobic activity significantly reduced the development of metastatic tumors in the lab models’ lymph nodes, lungs, and liver. The researchers hypothesized that in both humans and model animals, this favorable outcome is related to the enhanced rate of glucose consumption induced by exercise.

“Physical exercise, with its unique metabolic and physiological effects, exhibits a higher level of cancer prevention than any medication or medical intervention to date.” Dr. Yftach Gepner

From left to right: Prof. Carmit Levy and Dr. Yftach Gepner

“Exercise Changes the Whole Body”

“Our study is the first to investigate the impact of exercise on the internal organs in which metastases usually develop, like the lungs, liver, and lymph nodes,” explains Prof. Levy.

“Examining the cells of these organs, we found a rise in the number of glucose receptors during high-intensity aerobic activity – increasing glucose intake and turning the organs into effective energy-consumption machines, very much like the muscles. We assume that this happens because the organs must compete for sugar resources with the muscles, known to burn large quantities of glucose during physical exercise. Consequently, if cancer develops, the fierce competition over glucose reduces the availability of energy that is critical to metastasis.”

“Moreover,” she offers, “when a person exercises regularly, this condition becomes permanent: the tissues of internal organs change and become similar to muscle tissue. We all know that sports and physical exercise are good for our health. Our study, examining the internal organs, discovered that exercise changes the whole body, so that the cancer cannot spread, and the primary tumor also shrinks in size.”  

Prof. Levy emphasizes that by combining scientific knowhow from different schools at TAU, the new study has led to a very important discovery which may help prevent metastatic cancer – the leading cause of death in Israel.

“Our results indicate that unlike fat-burning exercise, which is relatively moderate, it is a high-intensity aerobic activity that helps in cancer prevention,” adds Dr. Gepner. “If the optimal intensity range for burning fat is 65-70% of the maximum pulse rate, sugar burning requires 80-85% – even if only for brief intervals.”

“For example: a one-minute sprint followed by walking, then another sprint. In the past, such intervals were mostly typical of athletes’ training regimens, but today we also see them in other exercise routines, such as heart and lung rehabilitation. Our results suggest that healthy individuals should also include high-intensity components in their fitness programs. We believe that future studies will enable personalized medicine for preventing specific cancers, with physicians reviewing family histories to recommend the right kind of physical activity. It must be emphasized that physical exercise, with its unique metabolic and physiological effects, exhibits a higher level of cancer prevention than any medication or medical intervention to date.”  

An innovative technology developed at Tel Aviv University will enable bone regeneration to correct large bone defects by means of a special hydrogel. Following successful tests in a lab model, the researchers now plan to move forward to clinical trials.

The groundbreaking study was conducted by experts from TAU’s Maurice and Gabriela Goldschleger School of Dental Medicine, led by Prof. Lihi Adler-Abramovich and Dr. Michal Halperin-Sternfeld, in collaboration with Prof. Itzhak Binderman, Dr. Rachel Sarig, Dr. Moran Aviv, and researchers from the University of Michigan in Ann Arbor. The paper was published in the Journal of Clinical Periodontology.

Prof. Adler-Abramovich: “Small bone defects, such as fractures, heal spontaneously, with the body restoring the lost bone tissue. The problem begins with large bone defects. In many cases, when substantial bone loss results from tumor resection (removal by surgery), physical trauma, tooth extraction, gum disease or inflammation around dental implants, the bone is unable to renew itself. In the current study, we developed a hydrogel that mimics the natural substances in the extracellular matrix of bones, stimulating bone growth and reactivating the immune system to accelerate the healing process.”

The researchers explain that the extracellular matrix is the substance surrounding our cells, providing them with structural support. Every type of tissue in our body has a specific extracellular matrix consisting of suitable substances with the right mechanical properties. The new hydrogel has a fibrillary structure that mimics that of the extracellular matrix of the natural bone. Furthermore, it is rigid, thus enabling the patient’s cells to differentiate into bone-forming cells.

WATCH: Lab of Bioinspired Materials: A Tour with TAU Prof. Lihi Adler-Abramovich

“As can be expected, the extracellular matrix of our bones is quite rigid,” says Prof. Adler-Abramovich. “In our study, we produced a hydrogel that mimics this specific matrix in both chemical and physical properties. At the nanometric level, the cell can attach itself to the gel, gaining structural support and receiving relevant mechanical signals from the fibers. At first, to test these properties, we grew cells in a 3D model of the gel. Then we examined the impact of the hydrogel on model animals with large bone defects that could not heal spontaneously. We monitored them for two months with various methods, including Micro C.T. To our delight, the bone defects were fully corrected through regeneration, with the bones regaining their original thickness, and generating new blood vessels.”

According to Prof. Adler-Abramovich, the innovative gel has extensive clinical applications in both orthopedic and dental medicine: “When we lose teeth due to extensive damage or bacterial infections, the standard treatment is dental implants. Implants, however, must be anchored in a sufficient amount of bone, and when bone loss is too substantial, physicians implant additional bone from a healthy part of the body – a complex medical procedure. Another option is adding bone substitutes from either human or animal sources, but these might generate an immune response. I hope that in the future the hydrogel we have developed will enable faster, safer, and simpler bone restoration.”  

Featured image: The research team

A new treatment developed at Tel Aviv University may significantly enhance the efficacy of chemotherapy in breast cancer patients, reducing the risk for lung metastasis following chemo from 52% to only 6%. Conducted in a lab model, the study identified the mechanism that generates a cancer-promoting inflammatory environment in response to chemotherapy. Moreover, the researchers found that by adding an anti-inflammatory agent to the chemotherapy, metastasis can be prevented.

The study was led by Prof. Neta Erez of the Department of Pathology at TAU’s Sackler Faculty of Medicine, and researchers from her group: Lea Monteran, Dr. Nour Ershaid, Yael Zait, and Ye’ela Scharff, in collaboration with Prof. Iris Barshack of the Sheba Medical Center and Dr. Amir Sonnenblick of the Tel Aviv Sourasky (Ichilov) Medical Center. The paper was published in Nature Communications. The study was funded by ERC, the Israel Cancer Association, and the Emerson Cancer Research Fund.

The Dark Side of Chemo

“In many cases of breast cancer, surgical removal of the primary tumor is followed by a chemotherapy regimen intended to kill any remaining malignant cells – either left behind by the surgeon or already colonizing in other organs,” explains Prof. Erez. “However, while effectively killing cancer cells, chemotherapy also has some undesirable and even harmful side effects, including damage to healthy tissues. The most dangerous of these, is probably internal inflammations that might paradoxically help remaining cancer cells to form metastases in distant organs. The goal of our study was to discover how this happens and try to find an effective solution.”

To this end, the researchers created an animal model for breast cancer metastasis. The animals received the same treatment as human patients: surgical removal of the primary tumor, then chemotherapy, followed by monitoring to detect metastatic relapse as early as possible. The disturbing results: metastatic tumors were detected in the lungs of a large percentage of the treated animals – similar to the percentage found in the control group.

“In humans, this interval between chemotherapy and detection of metastatic tumors is an inaccessible ‘black box.’ Working with an animal model, we could check what happens inside this ‘box’.” Prof. Neta Erez

 

What’s Going on Inside the “Black Box”?

To decipher these adverse effects, the researchers examined the animals’ lungs at an intermediate stage – when tiny micro-metastases may have already developed, but even advanced imaging technologies like CT cannot detect them.

“In humans, this interval between chemotherapy and detection of metastatic tumors is an inaccessible ‘black box’,” says Prof. Erez. “Working with an animal model we could check what happens inside this ‘box’.”

“We discovered a previously unknown mechanism: the chemotherapy generates an inflammatory response in connective tissue cells called ‘fibroblasts’, causing them to summon immune cells from the bone marrow. This, in turn, creates an inflammatory environment that supports the micro-metastases, helping them grow into full-fledged metastatic tumors. In this way, the chemotherapy, administered as a means for combating cancer, achieves the opposite result.”

The researchers also identified the mechanism through which fibroblasts recruit immune cells, and ‘train’ them to support the cancer. “We found that in response to chemotherapy, the fibroblasts secrete ‘complement proteins’ – proteins that mediate cell recruitment and intensify inflammation, often by summoning white blood cells to damaged or infected areas, a process called chemotaxis,” notes Prof. Erez. “When the immune cells reach the lungs, they create an inflammatory environment that supports cancer cells and helps them grow.”

 

“We identified an inflammatory mechanism through which chemotherapy inadvertently supports the growth of metastatic tumors, and also discovered an effective solution: combining chemotherapy with an inflammation inhibitor.” Prof. Neta Erez

Potential to Save Many Lives

To combat this newly discovered process, the researchers combined the chemotherapy administered to the animals with a drug that blocks the activity of complement proteins.

The results were very encouraging: following the combined treatment, the percentage of lab models developing no metastases rose from 32% to 67%; and the percentage of those with extensive cancer colonization in their lungs decreased from 52% with regular chemotherapy to 6% when the inflammation inhibitor was added.

“We discovered the mechanism behind a severe problem in the treatment of breast cancer: many patients develop metastatic tumors following removal of the primary tumor plus chemotherapy,” says Prof. Erez, and concludes: “We identified an inflammatory mechanism through which chemotherapy inadvertently supports the growth of metastatic tumors, and also discovered an effective solution: combining chemotherapy with an inflammation inhibitor. We hope that our findings will enable more effective treatment for breast cancer, and perhaps other types of cancer as well – to prevent metastatic relapse and save numerous lives worldwide.”  

Featured image: Members of the TAU research team (left to right): Dr. Nour Ershaid, Prof. Neta Erez and Lea Monteran

A first-of-its-kind study conducted by Tel Aviv University has found that the national resilience of the citizens of Ukraine, who are currently fighting for their independence, is comparatively very high (4.35) on a scale of 1 to 6. It is, in fact, significantly higher than the national resilience that characterized Israeli citizens (3.89) at the height of “Operation Guardian of the Walls” in May 2021.

The researchers explain this difference by saying that whereas Ukrainian citizens now find themselves fighting for their homeland and are ready to do anything to win the war, the rounds of fighting in Gaza have become a kind of recurrent nuisance for the citizens of Israel, accompanied by a moderate level of national resilience.

The study was led by Prof. Bruria Adini and Prof. Shaul Kimhi of the ResWell Research Center at Tel Aviv University’s Sackler Faculty of Medicine.

Ukrainian Citizens Still Have Hope

According to the researchers, the current study constitutes the first attempt by academic researchers to assess Ukrainian citizens’ positive and negative coping indices during wartime. The study indicates that in such conditions of conflict, a population may experience high levels of stress and, simultaneously, high levels of societal resilience and hope for the future.

In the current situation in Ukraine, the population has also demonstrated a great deal of support for their government.

The study surveyed 1000 Ukrainian citizens, as well as a sample of about 650 Israeli citizens using data collected during Operation Guardian of the Walls. The study’s findings suggest that the danger, in the eyes of Ukrainian citizens, is perceived as much more tangible (3.7 on a scale of 1 to 5) than Israelis’ perception of danger in the rounds of fighting against Hamas in Gaza (2.45). The perception of threat amongst Ukrainians is also more significant (3.29) than among the citizens of Israel (2.79).

The researchers note that the younger population, those between the ages of 26 to 30, present higher levels of stress and post-traumatic stress symptoms compared to other age groups. Women report higher levels of all negative coping mechanisms in comparison to men.

Interestingly, despite the significant dangers and threats they face, Ukrainian citizens have not lost hope, with their ‘hope index’ being higher (an average of 3.95) than that of Israelis (an average of 3.5).

“Israelis, unlike the Ukrainian People, do not feel that their country is under a direct existential threat and have, to a certain degree, adapted to an ‘emergency routine’ due to the recurrent conflicts.” Prof. Adini and Prof. Kimhi

Israelis Adapted to ‘Emergency Routine’

Prof. Adini and Prof. Kimhi explain that “the perception of a threat as existential to the survival and sovereignty of the state and society is likely, under certain conditions, to enhance the population’s societal resilience and sense of hope. This is the case even when the population feels anxious and threatened by the situation. “

“Moreover, it appears that the war launched by Russia against Ukraine has actually contributed to the process of Ukrainian identity-building, which also leads to increased levels of resilience, as well as an extremely high sense of hope.”

“Israelis, unlike the Ukrainian People, do not feel that their country is under a direct existential threat and have, to a certain degree, adapted to an ‘emergency routine’ due to the recurrent conflicts. In light of this, they present lower levels of resilience relative to Ukrainians, but at the same time higher levels of well-being and morale.”

Many young women with increased risk of breast cancer (carriers of BRCA1/BRCA2 genes) suffer from a state of uncertainty regarding their future, mainly due to the realization that they are highly likely to contract breast cancer and/or ovarian cancer. There is currently no effective treatment for preventing the illness and the only active procedure available is a risk-reducing mastectomy [surgery to remove a breast] and/or oophorectomy [a surgical procedure to remove one or both ovaries] around the age of 40 (it was this procedure that Angelina Jolie underwent in 2013).

Due to fear and uncertainty, these women often suffer psychological and physical symptoms that significantly disrupt their normal lives. In a new study conducted at Tel Aviv University, researchers sought to examine whether workshops and tools for promoting personal health, relief of stress and tension, and strengthening of mental soundness can improve the emotional well-being and quality of sleep of these young women. The researchers determined that use of the Inquiry Based Stress Reduction (IBSR) technique can be very helpful in coping with stressful events, enhance emotional and psychological well-being, improve quality of sleep, and assist in decision making.

Doing “The Work”

The study was led by Dr. Shahar Lev-Ari of the Sackler Faculty of Medicine at Tel Aviv University, in cooperation with Prof. Eitan Friedman of Sheba Medical Center and assistance from other researchers, as part of PhD student Clara Landau’s dissertation. The study was published in the prestigious medical journal JAMA Network Open.

The study included 100 women, all carriers of BRCA1/BRCA2 genes and currently under supervision at the Meirav Breast Center at Sheba Medical Center. As part of the study, the women learned and practiced the IBSR method, a clinical application of “The Work” by Byron Katie, consisting of a mindful self-inquiry for increased mindfulness, work on stress-causing beliefs (the “Inquiry” process) for reduction of stress, and cognitive reframing.

Dr. Shahar Lev-Ari

“To the best of our knowledge, this is the largest ever study in the world in the framework of such an experiment, as far as the number of participants is concerned.” 

Significant Improvements

The results were impressive. After participating in the workshops, as well as self-practice, the women showed great improvement in all aspects of personal growth, positive relations with others, life goals, and self acceptance. A clear improvement was seen in quality of sleep, which returned to normal.

Furthermore, a clear change of attitude was found among the participants with regard to previous doubts over whether to undergo surgical procedures such as mastectomy and oophorectomy. The technique helped the women make rational medical decisions, and some changed their position from ruling out the option of having any procedure done to scheduling a doctor’s appointment to discuss the option.

The researchers believe their findings indicate that study and practice of IBSR techniques might improve the psychological well-being of women with BRCA1/BRCA2 gene mutations, and form the basis (in conjunction with other studies) for recommending to consider providing this technique to women, along with their oncogenetic consultation.

“To the best of our knowledge, this is the largest ever study in the world in the framework of such an experiment, as far as the number of participants is concerned,” says Dr. Shahar Lev-Ari.

“We think that healthcare services in Israel and worldwide should evaluate the impact of coping with the genetic information and surgical procedures offered to asymptomatic women carriers on their emotional well-being and quality of life, and offer them interventions to promote their health on the individual level, such that have been scientifically proven in improving the quality of life and emotional well-being of women with the BRCA1/BRCA2 genes,” he summarizes.

Once melanoma, or skin cancer, spreads to the brain, it becomes extremely aggressive. Individuals with this stage of cancer are given an average 15 months to live, and that is following surgery, radiation, and chemotherapy. Researchers from Tel Aviv University deciphered, for the first time, a mechanism that enables skin cancer to metastasize to the brain and managed to delay the spread of the disease by 60% to 80% (depending on the stage of the intervention) using existing treatments.

The encouraging study was led by Prof. Ronit Satchi-Fainaro and Ph.D. student Sabina Pozzi of the Sackler Faculty of Medicine at Tel Aviv University. The results were published in the scientific journal JCI Insight.

“In an advanced stage, 90% of melanoma patients will develop brain metastases. This is a puzzling statistic. We expect to see metastases in the lungs and liver, but the brain is supposed to be a protected organ.”

How do the Cancer Cells Infiltrate the Brain?

“In an advanced stage, 90% of melanoma [/skin cancer] patients will develop brain metastases,” explains Prof. Satchi-Fainaro. “This is a puzzling statistic. We expect to see metastases in the lungs and liver, but the brain is supposed to be a protected organ. The blood-brain barrier keeps harmful substances from entering the brain, and here it supposedly doesn’t do the job—cancer cells from the skin circulate in the blood and manage to reach the brain. We asked ourselves with ‘whom’ the cancer cells ‘talk’ to in the brain to infiltrate it.”

The researchers found that in melanoma patients with brain metastases, the cancer cells “recruit” cells called ‘astrocytes’, star-shaped cells found in the spinal cord and brain which are responsible for maintaining stable conditions (/homeostasis) in the brain.

“The astrocytes are the first to come to correct the situation in the event of a stroke or trauma, for example,” says Prof. Satchi-Fainaro, “and it is with them that the cancer cells interact, exchanging molecules and corrupting them.”

Protecting the Brain’s Border Guards

“Moreover, the cancer cells recruit the astrocytes so that they do not inhibit the spread of the metastases. As such, they create local inflammation in the melanoma cells-astrocytes interaction areas that increase the permeability through the blood-brain barrier, as well as the division and migration of the cancer cells.”

“The communication between them is reflected in the fact that the astrocytes begin to secrete a protein that promotes inflammation called MCP-1 (also known as CCL2), and in response to this, the cancer cells begin to express its receptors CCR2 and CCR4, which we suspected to be responsible for the destructive communication with the astrocytes.”

“Both the antibody and the small molecule we used (…) have already been tested on humans as part of clinical trials. Therefore, these treatments are considered safe, and we can try to repurpose them for melanoma.”

To test their hypothesis, Prof. Satchi-Fainaro and her team tried to inhibit the expression of the protein and its receptors in genetically engineered lab models and in 3D models of primary melanoma and brain metastases. To this end, the researchers used both an antibody (biological molecule) and a small molecule (synthetic), designed to block the MCP-1 protein. They also employed CRISPR technology, a gene-editing technique, to genetically edit the cancer cells and cut out the two genes that express the two relevant receptors, CCR2 and CCR4. With each of the methods, the researchers were able to delay the spread of metastases.

“These treatments succeeded in delaying the penetration of the cancer cells into the brain and their subsequent spread throughout the brain,” says Prof. Satchi-Fainaro. The team succeeded in achieving a 60% to 80% delay, depending on the stage of the intervention. They achieved the best results with the treatment conducted immediately after surgery to remove the primary melanoma and were able to prevent the metastases from penetrating the brain.

“I believe that the treatment is suitable for the clinic as a preventive measure,” says Satchi-Fainaro. “Both the antibody and the small molecule we used—which are primarily intended to treat sclerosis, diabetes, liver fibrosis, and cardiovascular diseases, as well as serve as a biomarker for other types of cancer—have already been tested on humans as part of clinical trials. Therefore, these treatments are considered safe, and we can try to repurpose them for melanoma.”

The research was conducted in collaboration with additional scientists and physicians from Tel Aviv University, including Prof. Adi Barzel, Dr. Asaf Madi, Prof. Iris Barshack, Prof. Eran Perlson, and Prof. Inna Slutsky. International researchers also participated in the study, including Prof. Eytan Ruppin from the US National Institutes of Health (NIH), Prof. Henry Brem and Thomas Hyde from Johns Hopkins University-, and Prof. Helena Florindo from the University of Lisbon.

The study was funded by the European Research Council (ERC), the Melanoma Research Alliance (MRA), the Kahn Foundation, the Israel Cancer Research Fund (ICRF), and the Israel Science Foundation (ISF).

Featured image: Ph.D. student Sabina Pozzi and Prof. Ronit Satchi-Fainaro

A team of Tel Aviv University researchers has demonstrated that antibodies isolated from the immune system of recovered COVID-19 patients are effective in neutralizing all known strains of the virus, including the Delta and the Omicron variants. The discovery may eliminate the need for repeated booster vaccinations and strengthen the immune system of populations at risk.

The research was led by Dr. Natalia Freund and doctoral students Michael Mor and Ruofan Lee of the Department of Clinical Microbiology and Immunology at the Sackler Faculty of Medicine and of the TAU Center for Combating Pandemics. The study was conducted in collaboration with Dr. Ben Croker of the University of California San Diego. Prof. Ye Xiang of Tsinghua University in Beijing. Prof. Meital Gal-Tanamy and Dr. Moshe Dessau of Bar-Ilan University also took part in the study. The study was published in the Nature journal Communications Biology.

Highly Effective Against Delta and Omicron

The present study is a continuation of a preliminary study conducted in October 2020, at the height of the COVID-19 crisis. At that time, Dr. Freund and her colleagues sequenced all the B immune system cells from the blood of people who had recovered from the original COVID strain in Israel, and isolated nine antibodies that the patients produced. The researchers now found that some of these antibodies are very effective in neutralizing the new coronavirus variants, Delta and Omicron.

“In the previous study, we showed that the various antibodies that are formed in response to infection with the original virus are directed against different sites of the virus,” says Dr. Freund. “The most effective antibodies were those that bound to the virus’s ‘spike’ protein, in the same place where the spike binds the cellular receptor ACE2. Of course, we were not the only ones to isolate these antibodies, and the global health system made extensive use of them until the arrival of the different variants of the coronavirus, which in fact rendered most of those antibodies useless.”

“In the current study, we proved that two other antibodies, TAU-1109 and TAU-2310, which bind the viral spike protein in a different area from the region where most of the antibodies were concentrated until now (and were therefore less effective in neutralizing the original strain) are actually very effective in neutralizing the Delta and Omicron variants. According to our findings, the effectiveness of the first antibody, TAU-1109, in neutralizing the Omicron strain is 92%, and in neutralizing the Delta strain, 90%. The second antibody, TAU-2310, neutralizes the Omicron variant with an efficacy of 84%, and the Delta variant with an efficacy of 97%.”

Can Serve as Effective Substitute for Boosters

According to Dr. Freund, the surprising effectiveness of these antibodies might be related to the evolution of the virus: “The infectivity of the virus increased with each variant because each time, it changed the amino acid sequence of the part of the spike protein that binds to the ACE2 receptor, thereby increasing its infectivity and at the same time evading the natural antibodies that were created following vaccinations.”

“In contrast, the antibodies TAU-1109 and TAU-2310 don’t bind to the ACE2 receptor binding site, but to another region of the spike protein – an area of ​​the viral spike that for some reason does not undergo many mutations – and they are therefore effective in neutralizing more viral variants. These findings emerged as we tested all the known COVID strains to date.”

“In our view, targeted treatment with antibodies and their delivery to the body in high concentrations can serve as an effective substitute for repeated boosters, especially for at-risk populations and those with weakened immune systems.” 

The two antibodies, cloned in Dr. Freund’s laboratory at Tel Aviv University, were sent for tests to check their effectiveness against live viruses in laboratory cultures at the University of California San Diego, and against pseudo viruses in the laboratories of the Faculty of Medicine of Bar-Ilan University in the Galilee; the results were identical and equally encouraging in both tests.

Dr. Freund believes that the antibodies can bring about a real revolution in the fight against COVID-19: “We need to look at the COVID-19 pandemic in the context of previous disease outbreaks that humankind has witnessed. People who were vaccinated against smallpox at birth and who today are 50 years old still have antibodies, so they are probably protected, at least partially, from the monkeypox virus that we have recently been hearing about. Unfortunately, this is not the case with the coronavirus. For reasons we still don’t yet fully understand, the level of antibodies against COVID-19 declines significantly after three months, which is why we see people getting infected again and again, even after being vaccinated three times.”

“In our view, targeted treatment with antibodies and their delivery to the body in high concentrations can serve as an effective substitute for repeated boosters, especially for at-risk populations and those with weakened immune systems. COVID-19 infection can cause serious illness, and we know that providing antibodies in the first days following infection can stop the spread of the virus. It is therefore possible that by using effective antibody treatment, we will not have to provide booster doses to the entire population every time there is a new variant.”

Featured image: Dr. Natalia Freund from the Sackler Faculty of Medicine (Photo: Yoram Reshef)