Researchers created a composition of nanoparticles that was able to destroy lymphoma cells in mice
How and why do cells destroy themselves? Apoptosis is a process in which a pathological cell kills itself in a planned manner. This complex process occurs in every cell in the body and there are two mechanisms for its activation: through death receptors found on the cell membrane or through the mitochondria (an intracellular organelle that produces a significant part of the chemical energy needed for the body's cells, for their functioning and maintenance). Each of these mechanisms causes the activation of caspases - enzymes that carry out apoptosis. This system is tightly controlled by proteins that regulate apoptosis (which promote or inhibit cell death). In many cancer cells, the activity of death-inhibiting proteins increases, which gives them an advantage and makes them resistant to chemotherapy.
Researchers from Hadassah Ein Kerem Hospital and the Faculty of Medicine at the Hebrew University - Prof. Dina Ben-Yehuda, Prof. Shimon Benita, Dr. Taher Nassar, Dr. Ricky Perlman and Dr. Ihab Abdel Rahman - examine in their studies how cancer cells learn to escape apoptosis and thus Contribute to the development of malignant tumors.
What is the question? How can the cancer cells in lymphoma be treated without damaging the healthy cells?
"One of the malignant diseases we are investigating, which develops due to inhibition of apoptosis, is lymphoma. The lack of death of the lymphoma cells is the main reason for the slow development of the disease. And the lymphoma cells are resistant to chemotherapy because it is aimed at damaging their rapid division and not at creating apoptosis. Therefore, we sought to understand why the lymphoma cells do not die, what is the mechanism that allows them to do so," explains Prof. Ben-Yehuda.
The researchers discovered that one of the proteins that inhibits the death of lymphoma cells and other tumor cells, by inhibiting caspases, helps cells survive and helps tumors develop, is a protein called Livin (which belongs to a well-known protein family called IAP -Inhibitor of Apoptosis Proteins). According to Prof. Ben-Yehuda, "We realized that there is an interaction between the caspases and the Livin protein; This protein inhibits cell death, but under certain conditions - for example in contaminated or mutated cells that need to die - the caspases cut Livin and produce a new, small protein from it that not only does not inhibit apoptosis but also induces it, called tLivin."
Following this discovery, the researchers decided to focus on tLivin; They tested it in dozens of cancer cells (in test tubes, mice and human tumors) that are resistant to chemotherapy, and discovered that it promotes intense death.
In order to lead tLivin to cancer cells, in their latest study, which won a grant from the National Science Foundation, the research teams of Prof. Ben-Yehuda from Hadassah Ein Kerem and Prof. Benita from the Hebrew University joined together and created in Prof. Benita's laboratory nanoparticles that carry tLivin and in addition the molecule The CD40 protein as a possible treatment for lymphoma. The CD40 molecule was chosen because lymphoma cells have receptors for this protein. They then injected this bracelet into mice with lymphoma and discovered its effectiveness.
"The treatment was found to be effective against the lymphoma cells and significantly prolonged the survival of the mice. In addition, it was discovered as a potential treatment for lymphoma involving the nervous system (which chemotherapy is limited in treating). This is compared to mice with lymphoma that were not treated and died in a short time and compared to mice treated with a chemotherapy drug (doxorubicin), which was able to destroy the lymphoma cells but was toxic," explains Dr. Abdel Rahman.
We have developed an integrated drug delivery system with active proteins that can treat advanced cancer that is resistant to chemotherapy. The nanoparticles were designed and engineered to deliver drugs directly to the cancer cells.
According to Prof. Benita, "the goal of this study was to target tLivin in the cancer cells without harming the healthy cells. Therefore, we used nanotechnology and created a composition of tLivin and a CD40 ligand that was able to target only the cancer cells that overexpress the CD40 receptors. This is how we actually developed a possible treatment for lymphoma which is a type of blood cancer. We hope that treatments combining tLivin and CD40 ligand, with or without chemotherapy, trapped in nanoparticles will be tested in clinical trials in the future and will be part of personalized nanomedicine for cancer."
According to Dr. Nassar, "we have actually developed an integrated drug delivery system with active proteins that can treat advanced cancer that is resistant to chemotherapy. The nanoparticles were designed and engineered to deliver drugs directly to the cancer cells. This precision improves efficiency and reduces side effects. In addition, nanoparticles can gradually release drugs and thus enable personalized cancer treatment with improved results."
Life itself:
- Prof. Dina Ben-Yehuda, a doctor specializing in hematology, serves as a professor in the department of hematology at the Faculty of Medicine of the Hebrew University and the director of the hematology department at the Hadassah Medical Center. Until recently she also served as Dean of the Faculty of Medicine at the Hebrew University.
- Prof. Shimon Benita completed his bachelor's, master's and doctorate degrees at the School of Pharmacy of the Hebrew University and even managed it. He retired in 2016 ("I am in mock retirement; director of an active laboratory and a joint start-up with an application - the research development company of the Hebrew University"). His research focuses on drug delivery forms based on nanotechnology, microparticles and lipids. During his academic career he published more than 163 articles and chapters in scientific books, edited three books and issued 40 patent and patent applications.
- Dr. Ricky Perlman, completed her bachelor's, master's and master's degrees at the Hebrew University and post-doctoral training at the Massachusetts Institute of Technology (MIT). Manages Prof. Ben-Yehuda's research group and the hematology laboratory at Hadassah Ein Kerem Hospital.
- Dr. Ihab Abdel Rahman, completed a bachelor's degree at Ben Gurion University and a master's degree and doctorate in the department of human genetics at the Hebrew University School of Medicine. He managed projects in Prof. Ben-Yehuda's laboratory and is currently the director of the national unit for genetic editing in animals.
- Dr. Taher Nassar, completed a bachelor's degree twice (chemistry and pharmacy), a master's degree and a doctorate at the School of Pharmacy of the Hebrew University. Currently an associate and senior researcher in the Department of Pharmacy, director of a research laboratory and entrepreneur in start-up companies in Israel in the field of pharma, mainly the development of nanotechnology and the synthesis of drugs in the field of cancer, inflammatory diseases and obesity. Published over 62 scientific articles and 32 patent and patent applications.
More of the topic in Hayadan:
