Many Diseases will Disappear in the Future

From miniature biological chips that simulate the physiological activity of a human organ to smart nanoparticles and microdevices for delivering medicines, emerging technologies are enabling the treatment of diseases and studies that discern patterns that are beyond human capability

Imagine a world in which diagnosis and treatment of cancer is no longer a lengthy and exhausting journey of trial and error but rather, a swift, precise process, personalized for each patient. Imagine a world where chances of recovery are significantly increased and the side effects of the treatment decline dramatically. A world in which cancer is considered a chronic disease that people live with. This is the future that Prof. Ofra Benny and her team at the Hebrew University are striving to achieve, using breakthrough technologies such as miniature biological chips, a microdevice used as a research tool that simulates the physiological activity of a human organ or a combination of several organs (called “person on a chip). Instead of trying different treatments on the patients themselves, these technologies enable the researchers to simulate the reaction to dozens of different treatments simultaneously, on a miniature chip, and provide answers within few days. Other breakthrough technologies that Prof. Benny and her team are working on are “smart” nanoparticles that enable the delivery of drugs directly to the necessary organ without harming other organs, the use of smaller dosages, and other advantages. These nanomaterials are also the result of using AI tools that allow for precise designs of the particles and the engineering of materials that can respond to non-invasive physical means such as magnetism or optical tools.

Drugs that Destroy Damaged Blood Vessels

A significant turning point in Prof. Benny’s career was during her post-doctorate under the guidance of Prof. Judah Folkman, a pioneer in the field of angiogenesis in cancer. “Prof. Folkman discovered that cancerous tumors depend on blood vessels that they develop for themselves, and that one of the ways to combat a cancerous tumor is to create anti-angiogenetic drugs that destroy blood vessels”, she explains. “The idea opened a new world of possibilitiesfor fighting cancer via its supportive micro-environment – and for gaining a deeper understanding of the biological processes responsible for these complex diseases”.

This period also exposed Prof. Benny to the importance of the connection between academic research and the clinic, which enables an overview that incorporates both the practical contexts of industry and the clinical contexts”.

Tissue Engineering, Nanoparticles and Cancer

The multidisciplinary research laboratory that Prof. Benny leads today, integrates materials science, 3D printing, nanotechnology, and computing capabilities of AI and machine learning. “Because I engage in applied science, I regard the Innovation Authority as a very important springboard”, says Prof. Benny, who also mentions the commercialization company of the Hebrew University and Hadassah Medical Center. Many of my projects are now in commercialization stages and some have matured, either becoming or on their way to becoming startups. Almost all of them have a connection to the Innovation Authority: a third of them are currently in incubators. Each one of these projects, that are very focused on solving significant clinical challenges using bioengineering or bio-convergence, has the potential to become a breakthrough technology”, claims Prof. Benny.

Prof. Benny’s lab is developing several technologies that provide a solution via the holistic view of the cancerous tumor as a highly complex organism that includes, among other things, blood vessels, a 3D tumor, and communication between cells. The research is developing drugs that block blood vessels and impede the communication between the cells, and which act as efficient carriers of drugs.

From Skin Toxicity to Blindness

“The Innovation Authority’s investment helps in business and commercial aspects thereby enabling researchers to focus on the technological developments”, says Benny. Emris Pharma is one of the examples of companies established on the close connection between basic research and the clinic and was supported by the NGT Healthcare 2 Incubator. The research was started by Dr. Sharon Merims – a dermato-oncologist from Hadassah Ein Karem Hospital – who is exposed in her clinical work to the difficult struggle of cancer patients treated with biological drugs that incur serious dermatological side-effects that cause many of the patients to stop the treatment or reduce dosages.

The innovative solution developed by the company is based on unique delivery and drug systems. “We created nanoparticles loaded with a new drug that efficiently penetrates hair follicles, thereby neutralizing the skin’s side effects in the place with most toxicity. We are also working on other developments the objective of which is to maximize the optimal treatment for patients while successfully reducing suffering and the decline in quality of life”, says Prof. Benny. The company is approaching the end of its first year of activity and is expected to commence clinical trials in the coming years.

Orsight Pharma is another company within the same incubator born as the result of years of research by Prof. Benny together with Prof. Itay Chowers – the Director of the Department of Ophthalmology at Hadassah Medical Center. The company focuses on the development of an innovative treatment for eye diseases that cause irreversible blindness due to retina degeneration. “Following insights gained in the angiogenesis research, the company created an innovative family of tiny molecules that are safe for use and highly efficient in inhibiting the creation of blood vessels. The innovation lies in the active mechanism: the molecules work with a completely different biological mechanism from the one that currently exists in this field. The development is especially aimed at patients who do not respond to existing treatment (between 30%-50% of all patients) and offers them new hope, The company, that was only recently founded, has already shown promising results and is progressing to clinical trials, with the expectation of developing an innovative treatment within about two years.

A Revolution in Personalized Medicine for Cancer Patients

Pre-Cure, a company established two years ago, represents a significant breakthrough in the field of personalized medicine for cancer patients. At the core of its technology are biological chips that are based on microfluid systems. Over time, different methods have developed for 3D printing of biological chips that provide optimal simulation of the human body’s physiology. So far, the production of microfluid chips has been a long and complex process requiring sterile rooms and complex facilities. The creation of materials that are suitable for 3D printing also enables both safety for biological samples and optical transparency that facilitates microscopic observation. It also enables the production of complex designs that facilitate more detailed biological tests. The transition to printing enabled to truncate the process to only a few hours – instead of weeks. The technology allows the company to take biopsies of cancer cells from patients, to break them down to single cells and to create hundreds of replicas from them, including the patient’s unique tumor environment.

The clinical application of this revolutionary technology is already being assessed in a clinical feasibility study of different types of cancer, including head and neck cancer, ovarian cancer, bowel cancer, and others. The patient’s own cancerous replicas are used to scan drugs from a list of possibilities received from oncologists. Within a week, we can say which drug responded and how. This means a major step forward in personalized cancer medicine.

The platform gives doctors a very valuable decision-making support system, especially if the tumor returns, in the second and third line of treatments where the efficacy for the patient is not always obvious, and especially in cases where genomic analysis does not offer good enough solutions. We are working on parameters that simulate a physiological state – we grow the tumor tissue in 3D form and also preserve the flow so that the tumor experiences conditions that simulate the body in the patient’s specific biological context. The next step, already being worked on by the company, is to examine the sensitivity to radiation and the development of the immune system of this wonderful chip.

Pre-Cure recently joined the Innovation Authority’s ‘OrganoSpheres’ consortium that aims to examine and streamline 3D cell tests for personalized cancer treatment.

At the same time, Prof. Benny is leading a further innovative project that was previously supported by the Innovation Authority’s KAMIN Incentive Program in the field of drug delivery. “We are developing a medical device that releases medicine to the liver for treating liver cancer”, she explains. “We have developed porous microparticles that allow the localized and continuous release of a drug and subsequently enable to cause a blockage of the blood vessels and the degeneration of a liver tumor”. This project, which offers an advanced solution for treating liver cancer patients, is presently under a license agreement and expected to constitute the foundation of a new startup that will lead the unique clinical development for liver cancers.  

Science Fiction Becomes a Medical Device

Prof. Benny regards her work as an opportunity to empower emerging technologies and to advance the future of medicine. “In my mind’s eye, I see a future where the technologies converge. Technologies of human-machine interactions, a combination of biology and computation, and miniaturization capabilities that will lead to developments which were, until recently, considered science fiction”, she says, emphasizing the importance of integrating different fields, such as AI and nanotechnology, and their potential to generate a revolution in this field. “Today’s computational capabilities enable the examination of big data and to discern patterns that are beyond human capability. This also opens innovative horizons in the fields of engineering, materials, and medicine”.

Despite the numerous challenges, Prof. Benny is optimistic about the future: “Many of today’s diseases will disappear in the coming decades. Many of the types of cancer will become chronic diseases that people live with. This is just around the corner. Even though this is a complex task and there is still much to do, the treatment and identification capabilities already exist and can solve major human problems”.

In a world where technology is advancing at a dizzying speed, the combination of the researchers’ work, state support, and a long-term vision, can lead to breakthroughs that will change the face of medicine as we know it. With every miniature chip that is developed, we take another step towards a future in which diseases become a distant memory and the quality of life of millions of people will improve dramatically.