Nano-ghost, developed by Prof. Marcel Machluf, is an innovative technology that enables the focused internal delivery and release of anti-cancer drugs. This innovative delivery system is aimed at preventing side effects of chemotherapy and at dramatically enhancing the treatment's efficacy. The Nano-ghost system got its name from its modus operandi that includes emptying stem cells of their content, reducing them in the laboratory to nanometric size, transforming them into types of engineered delivery nano-systems (nano-ghosts), and loading them with different medicines. During the treatment, the patient is injected with these nano delivery systems loaded with the relevant medicines that make their way, via the blood vessels, to a specific tumor to release their important load.
Prof. Machluf is the dean of the Biotechnology & Food Engineering Faculty at the Technion and a world-renowned researcher in the fields of medicine delivery, gene therapy, cell therapy, and tissue engineering. "Stem cells know how to assign themselves to other types of cells and protect the body's immune system", she explains. "These cells treat infections and when there is no infection, the immune system 'relaxes' and is less focused on attacking the tumor".
In order to understand the interaction that develops between stem cells and the cells in the area of the cancerous tumor and the reason they remain there, Prof. Machluf and her team decided to investigate the nature of the human body, to transform the stem cells into "nanometric ghost cells" and to send them on their way, reduced in size, emptied of original content, and loaded with medication. The study they conducted revealed that at first the ghost cells wandered about the bloodstream but, upon sensing the cancer cells' signals, rushed within hours to the area under examination and went to work on the cancerous tumor with the medication they carried. "The nano-ghost cells acted as a 'trojan horse'", she explained, "and the cancerous cells, which thought that they were coming to their aid, let them in. The findings and the strong effect of the drugs were surprisingly good – the cancerous tumor shrunk after just a single injection of the nano-ghost".
Even Empty Nano-Ghost Cells Have an Effect
After conducting many experiments, the Nano-ghost team realized that the solution was a biological one, rather than chemical or synthetic. "In a biological system like ours, there is no need to assemble the molecule. We engineer the cell while it is still alive, before we turn it into a ghost, in a way that allows it to express the desired characteristics of the membrane. This is a tremendous advantage over other systems in which the specific molecule needs to be isolated and assembled with the right orientation. Nevertheless, choosing a biological solution also has a significant disadvantage – the cell production method is relatively limited, and it always takes a long time to analyze and characterize the medication. On an overall industry level, Nano-ghost's delivery system won't suit every type of medication because we cannot encompass and experiment with them all, but the delivery of those medicines that we do adapt will have a significant impact for the patients".
The results of Nano-ghost's experiments are positive and encouraging, and the delivery system has already been shown to be efficient against different types of cancers: "So far, we have worked only with animals but now need to find methods that are better suited for humans", she says. "Furthermore, we also need to find a way to increase the system's production capabilities, to characterize the nano-ghosts, and to meet the criteria required by the regulatory entities so that we can use the material and inject it into humans".
The lab team discovered that the ghost cells influence not only different kinds of cancer tumors but also other conditions. According to Prof. Machluf, "For example, when the cells are returned empty to the body, without medicines, they influence inflammatory systems that are created due to the appearance of cancer. The lab experiments have generated a lot of information and the company needs to focus on the desired pharmaceutical direction and on proving the system's feasibility – on whether to choose a drug that has been entirely unsuccessful, a successful drug with side effects that we can improve, or on a cancerous tumor for which no treatment exists. We are also looking for a solution for the Corona virus. The goal here is to transform our ghost cells into a trap for the virus. We intend to express the BCE2 receptor as a virus on the membrane's surface and only then to turn it into a ghost".
Clinical Trials Within Three Years
Nano-Ghost was officially founded in November 2019 following a complex phase of recruiting investors, but the process actually started three years previously. The professional team of employees emphasize the advantages of Bio-convergence: each comes from a different field on the engineering spectrum – biological, chemical, and physical. "Our vision is to commence clinical trials within 3 years and to start raising the necessary capital. We have accumulated a great deal of knowledge in using this system and we are currently focusing on the first stage of being able to conduct clinical trials that will prove that the system itself is not harmful or problematic", Prof. Machluf summarizes.
Until 2030 We Will Have a Solution for Most Types of Cancer
Groundbreaking thinking that creates synergy between different scientific fields is also a prominent characteristic of Prof. Avi Schroeder, a chemical engineer by training, who seven years ago founded a lab at the Technion for integrating nanotechnological solutions in medicine. Prof. Schroeder, who already has several startups and revolutionary developments in the fields of agriculture and precision medicine under his belt, estimates that mankind will solve most of its cancer-related problems within the next decade.
The basic underlying idea of Barcode Diagnostics – the company of which Prof. Schroeder is a founding partner, is the delivery and focus of medicines in liposomes – nanoparticles smaller than a cell from a human body – in order to lead it directly to the organ in need of treatment. The company has already successfully registered several patents related to this development.
"Creating a technology that provides a solution to problems in the fields of medicine or agriculture, has been one of the characteristics of my career", says Prof. Schroeder. "Barcode Diagnostics is an example of a company that was founded in response to a medical need, and where the technology was initially developed in academia. The Corona virus is presently highlighting to us all how medical challenges can paralyze a country and the world's economy. As far as I'm concerned, this is a wake-up call to all parties responsible for funding national R&D to relate to the developmental and production ability in the fields of biotechnology and pharmaceuticals as a strategic need".
Personalized, Precision, and Economic Mass Medicine
The major challenge facing the developers of pharmaceuticals and technologies is the need to join forces and connect all the relevant fields – essentially, bio-convergence. Prof. Schroeder believes that "today, contrary to the past, knowledge accumulated in research and medicine can be applied using artificial intelligence and be used to predict possible solutions. If we add to this our development and therapeutic ability, we can also combine robotics and nanotechnology to develop a new generation of more efficient smart medicines. Thanks to the combination of these fields, we can also lower development costs and reach a faster solution.
"In today's data-saturated age, the winning combination is that of economic mass medicine with personalized precision healthcare. The professionals know that different people react differently to disease and treatment, and this is especially true with diseases such as cancer where each patient experiences different intensities of the disease and treatment and reacts differently to medication. Research now has a better understanding of each patient's individual characteristics, but we still don't know how to provide for each person's specific medical needs. When we focus on personalized medicine, we will be able to heal better while also reducing suffering and side effects".
A Clear Indication Within 72 Hours
Barcode Diagnostics' development deals in precision medicine for cancer patients. "The company is developing a method to personally adapt drugs to treat cancer", says Ronen Eavri, CEO, and co-founder of Barcode Diagnostics. "Our method is aimed at identifying the optimal medication for each patient. The company intends to start a clinical study in breast cancer patients in 2021. Once we provide clinical evidence in breast cancer, the company will expand this technology platform to include additional cancer indications."
"The concept of the diagnostic method is similar to an allergy test where the doctor uses a low concentration of allergens and examines the body's allergic reaction. Using our diagnostic method, a tumor is injected with a tiny dosage of different medicines and the suitable treatment is then chosen according to the reaction. In this way, our development helps doctors receive a clear indication about the drug's efficacy and enables them to quickly make the optimal therapeutic decisions for each cancer patient in a personalized manner, while minimizing side effects and limiting the harm to healthy tissue.
"To deliver the medication, we use nanoparticles (liposomes) that are injected into the blood intravenously. In addition to the medicine, the nanoparticles also contain molecular barcodes that allow us to receive, within 72 hours, an indication regarding the cancerous cells that reacted to a specific medication and about each drug's degree of influence on the tumor. If the medication proves effective, we will detect an increase in the number of dead cells with specific barcodes in the tumor", Eavri explains.
Prof. Schroeder describes the development as a significant breakthrough: "The talented team at Barcode Diagnostics, located in Nazareth and Yokneam, creates the nanoparticles with the barcodes, and we are scheduled to conduct the first clinical trial in breast patients at the beginning of 2021. For this purpose, we are collaborating with clinicians from Israel and abroad who are helping us characterize the technology".
Breast Cancer Patients First
Barcode Diagnostics, which received financing from the Israel Innovation Authority, is preparing for the first clinical trial in breast cancer patients. The technology for delivering the drugs was initially developed at the Technion and the company's first steps towards foundation took place as part of the NGT3 Technology Incubator and with the support of the Innovation Authority. "We would not have been able to progress without the financial and organizational assistance of the Innovation Authority", says Eavri. "The incubator facilitated the early phases of our activity until we recruited the capital for the first clinical trial and a team that believed in the product".
At the same time, the company answered a call for proposals issued by the Innovation Authority regarding the Corona virus. "The initiative came from the employees", Eavri describes. "The main idea is to produce kits for mass-scale Corona testing that are based on the company's advanced diagnostic capabilities. The personal samples will be identified at DNA level by a unique barcode after which it will be possible to concentrate the individually labelled samples belonging to different subjects in a single test tube. This method enables us to save time and use an advanced device that can simultaneously scan tens of thousands of subjects tested each day. A specially designated team at the company took on the project and is trying to advance it towards commercialization after receiving the necessary regulatory approvals".
"The Bio-convergence revolution will lead to integrated developments that will generate a revolution in the treatment of cancer and other diseases", summarizes Prof. Schroeder. "Israel is in an excellent position to lead this revolution. Our scientists, engineers, and physicians are among the best in the world but our added asset is the ability to work together as a team, to combine our different fields – to bring the worlds of computing, artificial intelligence, robotics and nanotechnology into the world of medicine".
Dr. Ami Appelbaum, Chairman of the Israel Innovation Authority and Chief Scientist at the Ministry of Economy and Industry: "The global economy is currently undergoing one of its greatest crises, due in part to the inability to respond rapidly to and contend technologically with the threat of pandemics. Countries are desperate for new and rapid diagnostic technologies, for the capability to continuously monitor viruses and biological threats, to economize, and to accelerate the development of vaccines. These challenges mandate the creation of inventive engines of innovation. The world of Bio-convergence, which fuses biology and engineering, is the answer to this challenge and will be the next technological revolution of the 21st century".