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Vaccine boosting modifies CAR T cell metabolism and promotes crosstalk between CAR 
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BigField GEG Tech's insight:
Mass General investigators have created a new method that could make immune therapy more effective again brain tumors and expand its use against other types of solid tumors. Their study is published in the journal Nature Biotechnology.
Pierre-Luc Jellimann 's curator insight,
November 4, 2022 6:58 PM
Mass General investigators have created a new method that could make immune therapy more effective again brain tumors and expand its use against other types of solid tumors. Their study is published in the journal Nature Biotechnology. |
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In recent years, great advances have been made in the development of new successful immunotherapies to treat cancer. CAR T-cell therapy and antibody treatments are two types of targeted immunotherapies that have revolutionized areas of cancer care.
BigField GEG Tech's insight:
CAR T-cell therapy and antibody treatments are two types of targeted immunotherapies that have revolutionized the fields of cancer care. However, there are still significant challenges in identifying cancer cell surface proteins as targets for immunotherapies. A research group at Lund University in Sweden is well on their way as they have developed a new precision medicine technology that allows for comprehensive mapping of the entire tumor cell surface antigen landscape in patients. The method developed by the research team, "Tumor Surfaceome Mapping, TS-MAP," allows direct analysis of all accessible tumor cell surface antigens in patient tumor tissue. In a close collaboration between neurosurgery, oncology and advanced proteomics in Lund, the researchers were able to identify several tumor cell surface antigens in fresh tissue from patients with aggressive brain tumors for which there is currently no effective treatment. An important advantage of the TS-MAP technology is that it provides a complete picture of the cell surface antigens displayed on the surface of the cancer cell, as well as information about specific cell surface antigens that have a high capacity to infiltrate cancer cells, and can destroy them from within.
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Engineering T cells to destroy cancer cells has proved effective in treating certain types of cancer. However, it has not worked as well for solid tumors. One of the reasons for this lack of success is that T cells only target a single antigen. If some of the tumor cells don't express this antigen, they can evade T cell attack. In 2019, researchers found a way to overcome this obstacle, using a vaccine that enhances CAR-T cell efficacy. In a recent study, researchers wanted to investigate how this additional T-cell response is activated. The researchers discovered that in these vaccinated mice, metabolic changes occur in CAR-T cells that increase their production of interferon gamma, a cytokine that helps stimulate a strong immune response. This helps T cells overcome the tumor's immunosuppressive environment, which normally shuts down all T cells in the vicinity. As CAR-T cells killed tumor cells expressing the target antigen, host T cells encountered other antigens from these tumor cells, stimulating these host T cells to target these antigens and help destroy the tumor cells. Without this host T-cell response, the researchers found that tumors would regrow even if CAR-T cells destroyed most of them.