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New York Times
2 hours ago
- New York Times
Zelig Eshhar, Who Engineered Immune Cells to Fight Cancer, Dies at 84
Zelig Eshhar, an immunologist whose breakthrough research in the 1980s and '90s created a critical pathway to developing immunotherapies that attack particular cancers, died on July 3 at Tel Yitzhak, a kibbutz in central Israel. He was 84. The death was confirmed by Tova Waks, Dr. Eshhar's longtime research assistant, who said that Dr. Eshhar had been diagnosed with dementia and stopped working about five years ago. Dr. Eshhar's exploration of the human immune system began in the 1960s, during his Ph.D. studies at the Weizmann Institute of Science in Rehovot, near Tel Aviv, where he focused on the T-cell, a type of white blood cell with the natural ability to fight germs and disease. It does that by enlisting the help of 'a receptor that sits on the T-cell and binds with molecules of the foreign invader,' Dr. Eshhar told the Israeli newspaper Haaretz in 2017. 'The binding activates the T-cell's killer mechanism, which eradicates the alien cell. Eradication occurs, for example, when a virus invades a body cell.' But it doesn't always work. 'The mechanism by which the T-cell receptor identifies foreign molecules on cancerous cells and binds with them is not very efficient,' he said, 'so cancer cells occasionally evade them and develop in the body.' How, then, to improve the targeting ability of T-cells? Dr. Eshhar's solution was to create antibodies that target molecules characteristic of cancer cells. By combining those antibodies with T-cells, he was able to produce a hybrid known as a chimeric antigen receptor T-cell, or CAR-T, which can grab onto the proteins, called antigens, that appear on cancer cells. Dr. Eshhar shared the credit for this innovation with Ms. Waks, his technician, and a doctoral student, Gideon Gross, who were both named in the CAR-T patent. 'It was a tinkerer's dream: a way to rewrite the intricate machinery of these cells,' Scott Gottlieb, a former commissioner of the Food and Drug Administration, wrote in 'The Miracle Century: Making Sense of the Cell Therapy Revolution,' a book to be published by HarperCollins next year. 'Eshhar's invention was no minor tweak in the lab; it was a conceptual leap,' Dr. Gottlieb added. 'The notion that these genetically engineered immune cells could be re-engineered to home in on cancer transformed what once seemed a distant vision into an imminent reality.' Dr. Eshhar's CAR-T leap is the fundamental science behind immunotherapies that have been approved by the F.D.A. since 2017 to treat blood cancers like acute lymphoblastic leukemia, non-Hodgkin lymphoma and multiple myeloma. Small clinical trials of CAR-T therapies for ovarian and colorectal cancers have also shown promise, according to the National Cancer Institute. 'There's a direct line between Dr. Eshhar and these therapies,' Dr. Dan Littman, an immunologist at NYU Langone Health, said in an interview. 'It really was Eshhar who first showed that it could be done.' In an autobiographical essay provided by Ms. Waks, Dr. Eshhar wrote, 'Our biggest satisfaction was that CAR-T therapy was approved by the F.D.A., and now patients benefit by getting the treatment all over the world.' In an example of the possibilities offered by CAR-T immunotherapy, a study published last month in Journal of Clinical Oncology reported that 32 of the 97 patients with multiple myeloma, for whom immunotherapy was a last-ditch treatment, saw their cancers disappear and remain in remission after five years. The immunotherapy, developed by Legend Biotech, was delivered as 'an infusion of the patient's own white blood cells that have been removed and engineered to attack the cancer,' The New York Times reported. Cancer specialists say that CAR-T therapies have saved the lives of thousands of people with blood cancers. Zelig Lipka was born on Feb. 25, 1941, in Petah Tikva, in what was then the British Mandate of Palestine, and grew up in Rehovot. His parents were both from Poland; his father, Jacob, was a truck driver who brought agricultural products to market; his mother, Sarah, was a teacher. Zelig, who grew up in Rehovot, enlisted in the Israeli Army and joined a brigade on a kibbutz. After his military service, he stayed on at the kibbutz, where he started his scientific career as a beekeeper. A year later, he left to study biochemistry at Hebrew University of Jerusalem, where he earned a bachelor's degree in 1963 and a master's degree in 1966. The same year, he married Nomi Friedlander and changed his surname to Eshhar, the Hebrew word for a plant that grows in northern Israel. In 1968, he received his Ph.D. in chemical immunology from the Weizmann Institute of Science in Rehovot with a thesis on the role of T-cells. He went on to study at Harvard Medical School under Baruj Benacerraf, who would share the 1980 Nobel Prize in Physiology or Medicine for his discovery that the strength of an individual's immune response is controlled by a group of genes. At Harvard, Dr. Eshhar began to focus on cancer as a target for T-cells. 'Benacerraf discovered a distinctive molecule that characterizes the cancer cells, and he wanted to get a handle on it,' Dr. Eshhar told Haaretz in 2017. 'That was my task, and I gained recognition when I succeeded because no one had done it previously.' Dr. Eshhar returned to the Weizmann Institute as a research fellow in 1976 and became a senior scientist in 1979, an associate professor in 1987 and a full professor in 1994. He served as chairman of the department of immunology there from 1995 to 1998 and from 2002 to 2005. A journal paper he wrote on CAR-T in 1989, and a subsequent lecture, impressed Steven Rosenberg, the chief of the National Cancer Institute's surgery branch, who invited Dr. Eshhar to take a yearlong sabbatical in 1991 to help advance the institute's work on immunotherapy. 'Zelig's finding was clearly of enormous practical importance,' Dr. Rosenberg said during a panel discussion in Boston in 2022, when Dr. Eshhar was awarded the Richard V. Smalley Memorial Award from the Society for Immunotherapy of Cancer. Working with Dr. Patrick Hwu, a principal investigator, Dr. Eshhar applied his CAR-T model to ovarian cancer cells in mice, which led to a clinical trial. 'When you say CAR-T, it started with Zelig,' Dr. Hwu, who is now president of Moffitt Cancer Center in Tampa, Fla., said in an interview. 'And the first time we used that technology for any cancer was at the N.C.I.' Dr. Eshhar continued to focus on CAR-T research and other subjects at the Weizmann Institute and at the Tel Aviv Sourasky Medical Center, where he was named head of immunological research in 2012. In 2017, he told The Times of Israel that he wanted to improve CAR-T's 'specificity to certain kinds of cancer' and its use in fighting autoimmune diseases. Dr. Littman of NYU Langone Health said there had been recent success in clinical trials using CAR-T therapy to treat the autoimmune diseases lupus and scleroderma. 'It all tracks back to Eshhar's work,' he said. Dr. Eshhar received the Israel Prize in Life Sciences in 2015 and the Canada Gairdner International Award, recognizing research that improves human health, in 2024. He is survived by a son, Nir Eshhar, and two daughters, Sharon Eshhar Lavie and Meirav Shirion Eshhar, from his marriage to Ms. Friedlander, from whom he was separated; six grandchildren; three great-grandchildren; two brothers, Samuel and Eran; and a sister, Esther Cohen. Dr. Eshhar's domestic partner, Lihi Semel, died in 2017. In 2013, when the Weizmann Institute licensed Dr. Eshhar's patents for the CAR-T technology to Kite Pharma, Dr. Eshhar was paid $375,000; the biotechnology company was sold to Gilead Sciences in 2017 for $11.9 billion. At the time of the sale to Gilead, Kite said it had developed more than 10 therapies for various cancers using Dr. Eshhar's technology. Arie Belldegrun, the chairman of Kite, recalled after Dr. Eshhar's death that at the signing of the licensing deal in 2013, Dr. Eshhar inscribed a 50-shekel note to him and another board member, to mark 'a new beginning' for CAR-T therapy. 'Though small in size,' Dr. Belldegrun said in a statement on Oncodaily, a cancer news website, 'that note carries monumental symbolic value — a belief in a better future.'
CNN
3 hours ago
- CNN
In Pictures: Starvation in Gaza
Crowds form as Palestinians, including children, line up in Gaza City, Gaza, to receive food distributed by a charity on Tuesday. The World Food Program has warned that famine is looming, and 70,000 children in Gaza need urgent treatment for acute malnutrition. Ali Jadallah/Anadolu/Getty Images Two-year-old Yezen Abu Ful, who lives with his family in the Al-Shati refugee camp in northern Gaza, continues to lose weight. Pictured on July 13, his condition continues to worsen due to severe food shortages caused by the ongoing Israeli blockade. Ahmed Jihad Ibrahim Al-arini/Anadolu/Getty Images A 14-year-old Palestinian boy, Mosab Al-Debs, who is suffering from malnourishment, lies on a bed at Al-Shifa Hospital in Gaza City, on Tuesday. Dawoud Abu Alkas/Reuters Palestinian families and journalists gather in Gaza City to demand an end to Israeli attacks and the entry of humanitarian aid, on July 19. Demonstrators held banners reading "Gaza is starving," "Stop the attacks," and "We appeal to the world's conscience." Saeed M. M. T. Jaras/Anadolu/Getty Images
CNN
3 hours ago
- CNN
In Pictures: Starvation in Gaza
Crowds form as Palestinians, including children, line up in Gaza City, Gaza, to receive food distributed by a charity on Tuesday. The World Food Program has warned that famine is looming, and 70,000 children in Gaza need urgent treatment for acute malnutrition. Ali Jadallah/Anadolu/Getty Images Two-year-old Yezen Abu Ful, who lives with his family in the Al-Shati refugee camp in northern Gaza, continues to lose weight. Pictured on July 13, his condition continues to worsen due to severe food shortages caused by the ongoing Israeli blockade. Ahmed Jihad Ibrahim Al-arini/Anadolu/Getty Images A 14-year-old Palestinian boy, Mosab Al-Debs, who is suffering from malnourishment, lies on a bed at Al-Shifa Hospital in Gaza City, on Tuesday. Dawoud Abu Alkas/Reuters Palestinian families and journalists gather in Gaza City to demand an end to Israeli attacks and the entry of humanitarian aid, on July 19. Demonstrators held banners reading "Gaza is starving," "Stop the attacks," and "We appeal to the world's conscience." Saeed M. M. T. Jaras/Anadolu/Getty Images
