Patients with recurrent blood cancers such as leukemia or other hard to treat diseases have found an immunotherapy that supercharges the immune system's natural killing cells effective. Researchers at Washington University School of Medicine, St. Louis, have demonstrated that cell-based immunotherapy can also be used to treat solid tumors. They started with melanoma which is a deadly type of skin cancer.The study was published in Clinical Cancer Research (a journal of American Association for Cancer Research) on June 29th.Immunotherapy, also known as immune checkpoint inhibitors, has been a revolution in the treatment of advanced melanoma. This immunotherapy was used to successfully treat Jimmy Carter's melanoma, which had spread to his brain and liver.The therapy is only effective in half of these patients. Even those who do respond to the initial treatment, approximately half develop resistance to it. Researchers have explored other ways to use the immune system to fight melanoma cells. Natural killer (NK) cells could be used as a first line of defense against cancer cells and invading bacteria.Professor of Medicine, Todd A. Fehniger, MD and PhD have achieved success in clinical trials for recurrent leukemia using either patient's natural killer cells or donor cells. The NK cells are taken from a patient or a donor and then exposed to a series of chemical signals known as cytokines. These signals activate the cells and prime them for future activations. These "cytokine-induced memory like" NK cells can be given to patients to fight cancer. They are already more powerful, according Fehniger.Fehniger, who was the study's senior author and is an oncologist who sees patients at Siteman Cancer Center at Barnes-Jewish Hospital as well as at Washington University School of Medicine, said that "these'revved-up" memory-like NK cell attacks blood cancers quite effectively." However, very little research has been done to determine if these cells could be used against solid tumours. This is a gap in solid tumor treatment. This study proves that memory-like NK cell responses are better than normal NK cell responses against melanoma. It also serves as a steppingstone to a first in-human clinical trial with these cells in advanced melanoma.Ryan C. Fields MD, co-author, is the Kim and Tim Eberlein Distinguished Prof of Surgical Oncology. He said: "We hope that this will also be a step towards harnessing NK cell against multiple solid tumours. Because we know that it responds to immune treatment, melanoma was an ideal place to start. We felt that targeting an alternative part of the immune system would be a promising strategy, as many patients are unable to respond or develop resistance.Standard immunotherapy against checkpoints that works in some patients with melanoma targets T cells. This is another type of immune cell that can be harnessed to fight different types of cancer. The researchers found that patients who are not responding well to standard T cell-based therapy or don't respond to it and have no other options, would be a good candidate for NK cells therapy.Researchers studied human NK cell samples from healthy individuals and patients with melanoma. They found that cytokine-induced memory NK cells could be used to treat human melanoma-related tumors in mice. The tumors disappeared in most mice and were almost invisible for 21 days. The memory-like NK cell treatment prevented them from coming back in most cases. Normal NK cells did not reduce or control melanoma tumours in the same way.Fehniger stated that a clinical trial is being planned to test these NK cells in advanced melanoma patients who have exhausted all other options. "We would like NK cells from a donor as well as NK cells taken from a patient to determine if cytokine-induced memory-like NK cell therapy is an effective treatment option.The NK-cell-based immunotherapy can be safer than other cell-based immunotherapies. This is because the NK-cells do not cause a cytokine hurricane, which is sometimes seen in CAR-T cell therapy.Fields, a Siteman surgeon, stated that 10 years ago there were no effective treatments for advanced melanoma. This is similar to the lack of therapies today for glioblastoma and advanced pancreatic cancer. Although checkpoint immunotherapy has revolutionized the treatment of melanoma, we are still not satisfied by the 50% response rate. This NK cell therapy looks promising. We are determined to improve. We may also be able to combine NK cell-based therapy and checkpoint inhibition in the future for a better response.Fehniger, along with his colleagues, worked with Washington University’s Office of Technology Management in order to license the cytokine induced memory-like NK cells technology to a company called Wugen. Fehniger was a co-founder and member of the scientific advisory board for Wugen.###Fehniger, a consultant, and Melissa M. Berrien–Elliott (D.Ph.D., an instructor of medicine), are co-authors. They may also receive royalties income based upon technology they have developed that was licensed to Wugen by Washington University.The National Institutes of Health funded this work with grant numbers T32HL007088, R01CA248277 and R01CA205239. CCSG P30CA091842, K12CA167540, NIHU54CA224083, CCSG P30CA091842, CCSG P30CA091842, NIHU54CA224083, NIHU54CA224083, and SPORE in Leukemia, P50CA171063. Sidney Kimmel Translational Science Scholar Award, a Society of Surgical Oncology Clinical Investigator Award, the David Riebel Cancer Research Fund, the Leukemia and Lymphoma Society, the V Foundation for Cancer Research, and the AAI Intersect Fellowship program for Computational Scientists and Immunologists provided additional funding. The Washington University School of Medicine Surgical Oncology Basic Science and Translational Research Training Program grant number T32CA009621 was awarded by the National Cancer Institute. Siteman Flow Cymetry Core, the Immune Monitoring Lab, the Siteman Tissue Procurement Core and the core grant/services from the Washington University Digestive Diseases Research Core Center grant number P30 K052574 provided additional support.Marin ND, et. al. Memory-like differentiation increases NK cell responses in melanoma. Clinical Cancer Research. June 29, 2021The 1,500 Washington University School of Medicine faculty physicians are also the medical staff of Barnes and St. Louis Children's Hospitals. U.S. News & World Report consistently ranks the School of Medicine as one of the best medical schools in the country for teaching, research and patient care. The School of Medicine has been linked to BJCHealthCare through its affiliations with St. Louis Children's and Barnes-Jewish hospitals.
