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Registration Number

0224U002967, 0122U002453 , R & D reports

Title

Combined use of dendritic cells and photocontrolled analogues of natural cytotoxic peptides for immunotherapy of malignant neoplasms

Head

Khranovska Natalia M., к.б.н.

Registration Date

19-03-2024

Organization

National Cancer Institute

Description

The object of research is photocontrolled analogs of cytotoxic peptides, tumor cell lines, dendritic cells. The technology of loading generated in vitro dendritic cells with lysate of MDA-MB-231 tumor cells treated with cytotoxic peptides (CP) was developed. In the studies, 2 CPs were used - diarylethene-containing analogues of gramicidin S LMB002 and LMB033, each in closed and open forms. It was determined that the optimal concentrations for LMB002 and LMB033 (both in open and closed forms) are 16 and 32 µM, at which the death of tumor cells by immunogenic means is observed. The most optimal approach for obtaining lysates of tumor cells is 5 cycles of freezing to minus 200C and thawing at 560C, in which we obtained the necessary protein concentration for loading dendritic cells. The technology for obtaining mature dendritic cells included the loading of lysate cells of the MDA-MB-231 tumor line treated with LMB033 and LMB002 peptides on the 6th day of cultivation. The concentration of CP per 1x107 tumor cells was 16 or 32 ng/ml, the incubation time was 6 hours, the number of devitalized tumor cells after exposure to peptides was 90%. It was established that loading dendritic cells with lysates of MDA-MB-231 tumor line cells treated with peptides LMB033 and LMB002 contributes to a significant increase in the level of expression of the surface marker CD83, which indicates an increase in the degree of maturity of the generated dendritic cells. However, it should be noted that the use of CP caused a multidirectional effect on the antigen-presenting properties of cells depending on the form of the peptide (closed or open). We found that the closed form of LMB033 in concentrations of 16 or 32 µM promotes an increase in the level of costimulatory molecules CD86 and HLA-DR. Then, the open form of LMB033 at a concentration of 32 µM caused some inhibition of the antigen-presenting properties of dendritic cells, namely, the expression of CD86 and HLA-DR on them was significan

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Horbach Oleksandr I.
Skachkova Oksana V.