Engineered Removal of PD-1 From the Surface of CD19 CAR-T Cells Results in Increased Activation and Diminished Survival
A promising approach in tumor therapy is the use of T cells armed with the recombinant Chimeric T cell Receptors (CAR). Unfortunately, the CAR-T cell therapy is effective currently only for the treatment of hematologic malignancies. The major issue that limits practical usefulness of the CAR-T technology is cancer microenvironment, which suppresses activation of the CAR-T cells. A collaboration of scientists from IBCh RAS and other Russian and foreign institutes has modified T cells with CD19-CAR and reduced the expression PD-1 at the same time. Unexpectedly, despite increased activation of CAR-T cells with low level of PD-1, these T cells had reduced survival and diminished cytotoxicity. This work was supported by the Ministry Education and Science of the Russian Federation (Grant No. 075-15-2020-773) and published in Frontiers in molecular biosciences. Learn more
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The team of the Department of metabolism and redox biology of Institute of Bioorganic Chemistry in collaboration with colleagues from the Federal Center of Brain Research and Neurotechnologies of the Federal Medical Biological Agency, Lomonosov Moscow State University and several other institutes have developed a technology that allows real time recording of intracellular metabolic processes in vivo. On the model of ischemic stroke in rodents, the new data were obtained on changes occurring in neurons during the development of pathology.
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To reduce side effects in the process of oncotherapy, it seems promising to use two-step targeting delivery of active agents, or pre-targeting: at the first stage, a non-toxic targeting module (also including antibody or non-immunoglobulin scaffolds) is selectively delivered to a cell of a certain molecular profile, and at the second stage, a cytotoxic agent capable of specifically interacting with the first module is administrated into the organism.
- Antigen-specific stimulation and expansion of CAR-T cells using membrane vesicles as target cell surrogates
Development of CAR-T therapy led to immediate success in the treatment of B cell leukemia. Manufacturing of therapy-competent functional CAR-T cells needs robust protocols for ex vivo/in vitro expansion of modified T-cells. In this work, a team of scientists from the IBCh RAS in collaboration with a group of scientists from Dmitry Rogachev National Medical Research Center and colleagues from the Faculty of Biology of Moscow State University have created a new technology for the expansion of CAR T cells using artificial vesicles carrying surface tumor antigens. This approach will allow in the future to obtain CAR T-cells with improved functional properties and to minimize the level of premature "exhaustion" of the CAR T-cell population.