Ludwig Cancer Research scientists have devised new types of chimeric antigen-receptor (CAR) T cells-;a type of cancer immunotherapy-;that can be switched on to varying degrees of intensity and then switched off on demand with existing drugs.
Ludwig Cancer Research Oct 21 2024 Ludwig Cancer Research scientists have devised new types of chimeric antigen-receptor T cells-;a type of cancer immunotherapy-;that can be switched on to varying degrees of intensity and then switched off on demand with existing drugs.
The trouble is that many solid tumor antigens are found on healthy cells as well, raising the risks of so-called "off-tumor, on-target" effects. These can provoke destructive immune responses that are difficult to control and potentially lethal to the patient.
The latter possibility stems from studies-;led by Ludwig Stanford's Crystal Mackall-;showing that giving CAR-T cells periods of rest between bouts of active tumor targeting rewrites their gene-expression programs, reverses exhaustion and broadly boosts their functional efficacy. To enable control of CAR activity, Irving, Giordano Attianese and colleagues separated the antigen-sensing moiety and the activation domain on two separate chains, the 'receptor chain' and the 'signaling chain'. Tapping the expertise of Bruno Correia of the École Polytechnique Fédérale de Lausanne , they also included an extra module able to dimerize the two chains upon application of a cancer drug called venetoclax.
Cancer Immunotherapy Immunotherapy Antibody Antigen Blood CD3 Cell Drugs Efficacy Exhaustion Ion Molecule Preclinical Protein Receptor Research Tumor
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