The New Dawn of Immunotherapy

THE BIOMEDICAL OPINION OPINION THE BIOMEDICAL 16 SCIENTIST One-to-one One-to-one SCIENTIST 17 Left. ACT using autologous lymphocytes targeting somatic mutations undergone one of the most rare events in medicine – a spontaneous regression.” Steven felt the explanation for this had STEVEN ROSENBERG THE NEW DAWN OF to be buried somewhere in the patient’s Chief of surgery at the immune system. “The body has hundreds National Cancer Institute of billions of lymphocytes,” he says, “and in Bethesda, Maryland Pre-treatment 14 Months IMMUNOTHERAPY somewhere in the body of the patient BA and MD degrees at there had to be lymphocytes that could Johns Hopkins University, Steven Rosenberg made headlines around the recognise what was different about the PhD in Biophysics at respond to all previous chemotherapy and unique mutations in a patient’s cancer globe for a breakthrough that could make cancer. This led us to identify the cells Harvard University hormonal treatment. can result in dramatic durable that were attacking the cancer and then Residency training in Steven describes his new technique as regressions,” says Steven. “This breast immunotherapy a frontline cancer treatment. use them to develop a cancer treatment.” surgery at the Peter Bent “a high-throughput method to identify cancer patient is now cancer-free based Steven and his colleagues subsequently Brigham Hospital in Boston, mutations present in a cancer that are on all available studies two-and-a-half isolated various types of immune cells Massachusetts recognised by the immune system. But years after treatment.” he idea of immunotherapy, century, it began to reawaken. A key and, in a series of early trials, injected Developed the first effective because this new approach to or modifying the body’s own breakthrough came in 1976 with the them into patients. Initially, success immunotherapies and gene immunotherapy is dependent on Way forward defence mechanism to fight discovery of how to produce in vitro eluded them, but in 1984 they gave their therapies for patients with mutations, not on cancer type, it is in a It’s an outcome that he hopes will point diseases such as cancer, cultures of T lymphocytes – otherwise 67th patient a far higher dose of T cells. advanced cancer sense a blueprint we can use for the the way forward for immunotherapy: dates back to the 1890s and known as T cells, or the white blood cells She responded to the treatment and is Studies of cell transfer treatment of many types of cancer”. “This approach holds the best the pioneering work of US that adapt the body’s immune response to still alive today. immunotherapy have It amounts to a modified form of opportunities for finding effective surgeon William Coley, who specific threats. resulted in complete adoptive cell transfer. This has immunotherapies for patients with the established a link between Frontline treatment? remissions in patients with successfully treated cancers with high solid cancers. I have showed the slides metastatic melanoma bacterial infections in cancer patients, Miraculous event The key was to perfect the technique of levels of mutations, such as melanoma, (pictured) at two American Association Ttheir immune response to those Steven Rosenberg, then a young surgeon, extracting T cells from a patient’s body Recent studies lung and bladder cancers, but has been of Cancer Research meetings, and have infections, and the subsequent remission now Chief of Surgery at the US National and growing them by the billions in the have seen less effective with cancers that start in shown that about 80% of patients with regressions of their cancer. Coley developed a Cancer Institute (NCI) Center for Cancer lab. This has yielded increasingly positive the lining of organs, such as stomach, common epithelial cancers have T of metastatic prototype treatment, known as Coley’s Research, was involved in the work that results, but it’s the outcome of their latest ovarian, and breast cancers, and have lymphocytes reactive against their own cancer in toxins, but this was soon outpaced by new built on this discovery. His interest in clinical trial, published in Nature Medicine, patients with lower levels of mutations. cancer, and that of the 197 immunogenic surgical techniques and the emerging immunotherapy had started early in his that suggests a breakthrough that could sarcomas recognised mutations 196 were unique to technology of radiotherapy. career, when he met a young cancer see immunotherapy become a frontline and Targeting tumours the patient’s cancer and not shared by any The promise of immunotherapy lay patient whose tumours has disappeared treatment for cancer. lymphomas. Steven and his team used tumour- other patient.” dormant for decades, but as biomedical without treatment. “All aspects of his Their subject was a patient with infiltrating lymphocytes (TILs) from the Steven feels this insight should change science advanced during the 20th cancer had gone,” says Steven. “He had metastic breast cancer who had failed to patient, which, as their name suggests, the way cancer is treated: “We need a new specifically target tumour cell mutations. paradigm for cancer therapy. Highly Their first step was to identify the personalised treatments are likely to be patient’s unique cell mutations by necessary to make progress in treating sequencing DNA and RNA from her common cancers. A unique drug for each normal tissue and her tumours. They patient may be needed. Many oncologists found 62 different mutations. Next, they think this is not practical. I think a drastic tested the TILs to pick out those that change is needed and I now know of at recognised one or more of her mutated least three companies that are working proteins. The job was then to grow these to try to develop this commercially.” TILs in sufficient numbers in the lab and Almost 130 years after William inject them back into the patient in order Coley first suggested the idea of to create a much more powerful immune immunotherapy, Steven and his team response against her individual tumours. have shown that its inherent biological Her cancer is now in full regression. complexities can be overcome, and in “For multiple cancer types that are the process have taken a giant leap refractory to all known chemotherapies towards to a personalised treatment for IMAGES: SHUTTERSTOCK/NATIONAL CANCER INSTITUTE and immunotherapies, attacking the a personalised disease. .

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