Registration Number
0223U002433,
0122U002453
, R & D reports
Title
Combined use of dendritic cells and photocontrolled analogues of natural cytotoxic peptides for immunotherapy of malignant neoplasms
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Head
Khranovska Natalia M., к.б.н.
Registration Date
21-02-2023
Organization
National Cancer Institute
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The object of research is the cytotoxic activity of photocontrolled analogs of cytotoxic peptides, the release of adenosine triphosphate. The goal of the project stage is to develop methodical approaches to obtaining a lysate of tumor cells through their immunogenic death under the action of PCP, which have optimal properties in terms of photoswitching efficiency and the level of activation of the immune system by them. Research methods – cell culture, cytofluorimetric, luminescent, statistical. The research used 2 cytotoxic peptides (CP) - diarylethene-containing analogs of gramicidin S LMB002 and LMB033, each in closed and open forms. As a result, a methodical approach to obtain lysate of tumor cells of the CLL line under the influence of CP was developed. The optimal number of CPUs and the time of their treatment of tumor cells were established. When using CP at a concentration of 16 µM and under conditions of exposure to tumor cells for 30 minutes, 40-60% of dead cells in cultures were registered when using closed forms of peptides, and 85% when using open forms. The use of CP at this concentration promoted maximal ATP release. At the same time, the open forms of the peptides contributed to a significant increase in the generation of ATP in tumor cells in comparison with both the action of the corresponding closed form and DMSO. Thus, it was established that the cytotoxic activity of CP in its open form is accompanied by the immunogenic death of tumor cells of the CLL lineage. The obtained facts can serve as a basis for the use of open forms of CP in schemes of combined cancer immunotherapy and as a component in the technology of manufacturing anticancer drugs. In particular, the technology of obtaining lysate of tumor cells under the action of open forms of CP will be used for the development of new technologies for loading dendritic cells (DC) in the creation of innovative antitumor immunotherapeutic drugs based on them.
Product Description
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Gorbach Olexandr I.
Skachkova Oksana V.
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2023-02-21
