Additionally, he is investigating the effect of chemotherapy on the metabolic status of T cells in order to define therapeutic interventions to maintain T-cell efficacy for immunotherapy in the face of chemotherapy. This innovative approach to understanding how to enhance CAR T-cell production is shedding urgently needed light on the process of CAR T-cell generation. Metastasis to the liver is a major cause of morbidity and mortality associated with a wide range of cancers, including gastrointestinal GI malignancies such as pancreatic ductal adenocarcinoma PDAC.
However, outcomes vary tremendously among different patients, and positive effects often do not last very long. In gastrointestinal malignancies, for instance, metastasis to the liver is common and associated with poor responsiveness to immunotherapy. In pancreatic cancer, which is predicted to become the second-leading cause of cancer-related deaths by , the liver is directly exposed via the portal vein to soluble factors and antigens released by developing tumors.
Preliminary work from the Beatty lab has found that the immune microenvironment in the liver is conditioned early during pancreatic cancer development. This results in a liver that displays enhanced susceptibility to metastasis. Based on these findings, Beatty hypothesizes that the immune microenvironment in the liver is inherently malleable; it has the capacity to support or suppress antitumor immunity. During cancer development, the microenvironment is induced to favor cancer cell metastasis and limit the efficacy of cancer immunotherapy.
With this grant, Beatty is testing this idea and trying to better understand the exact mechanism by which the liver may regulate the efficacy of immunotherapy. Acute myeloid leukemia AML is a frequently fatal blood cancer with a number of subtypes, many of which have characteristic abnormalities in certain genes and proteins.
The past few years have seen the development of several new and exciting types immunotherapy, including infusions of T cells, a category of immune cells that can be engineered to recognize and kill cancer cells.
Unfortunately, most of the T-cell immunotherapies available today are not suitable for AML because the proteins on the surface of cancerous AML cells are similar to the proteins on the surface of normal blood and bone marrow cells, leading to severe side effects when T-cell immunotherapy also targets these normal cells.
To address this issue, Bleakley is working to develop immunotherapy that targets abnormal cancer-specific proteins inside the cell rather than the less specific proteins on the cell surface. The ultimate goal of this study is to harness the discoveries from this project to develop innovative T-cell immunotherapies and therapeutic vaccine candidates for preclinical and, eventually, clinical testing.
Immunotherapy has brought a sea change to how cancers are treated, with the potential for complete recovery from cancers with otherwise low survival rates. Among those therapies, CAR T-cell therapy has shown dramatic activity in several hematological cancers, including advanced, chemotherapy-resistant acute lymphoblastic leukemia ALL. T cells, a type of white blood cell that scans the bloodstream for cellular abnormalities and infections, have been engineered with chimeric antigen receptors CARs that target tumor-associated antigens.
Immunotherapy is a pioneering new treatment which boosts the body's own natural defences to fight cancer. Showing spectacular success in trial phases, it often has fewer debilitating side effects than chemotherapy, allowing patients to go 'cancer incognito' in their daily lives. The film will also follow the group in-between treatment sessions - for an intense summer of love, laughter and living, not 'fighting'.
Challenging common preconceptions about what cancer patients and cancer treatments look like, the documentary will follow these patients as they discover whether the immunotherapy is working or not, and whether it has given them the most precious gift of all: more time. Their treatment will take place at the internationally renowned The Royal Marsden NHS Foundation Trust in London, a world-leading specialist cancer hospital that treats more than 50, cancer patients a year.
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