Published online: 2018-12-31
DOI: 10.24075/brsmu.2018.091
Cancer immunotherapy with T-cells that carry chimeric antigen receptors is currently on cutting edge of modern oncology. Autotransplantation of T-lymphocytes with chimeric receptor specific for certain tumor antigen proves to be clinically effective, but costly. Linear carriers of chimeric antigen receptors based on natural killer NK-92 cell culture may be an affordable alternative, however, this culture is resistant to lentiviral transduction. Recently, lentiviral vectors, pseudotyped with surface glycoproteins of the measles virus vaccine strain, have recently been successfully applied for transduction of primary immune cells. The aim of the work was to assess the efficiency of transduction of NK-92 cells with lentivirus vectors, pseudotyped with measles F and H surface glycoproteins, as well as to establish optimal conditions for selection of NK-92 transduced with the chimeric receptor against CD20 and to evaluate the culture’s cytotoxic potential. The results showed that the maximum infectious titer is achieved using the H∆18 variant in combination with F∆30, and the use of the TBK1/IKKɛ inhibitor BX795 results in additional 3-fold increase in the infectious titer. CAR-expressing NK-92 were able to suppress the proliferation of CD20+ cell line Raji in lower effector-to-target ratios than unmodified NK-92.
VIEWS 45
Published online: 2018-12-31
DOI: 10.24075/brsmu.2018.089
Radionuclide therapy (RNT) is an effective modality for treating multiple metastases in patients with cancer. The list of malignancies that can be managed with RNT expands with the arrival of novel tumoritropic radiopharmaceuticals (RP). A versatile delivery platform capable of carrying various therapeutic and diagnostic radionuclides, as well as vector molecules needed to achieve sufficient specificity to tumor cells and ensure therapeutic efficacy may hold great promise for radiation therapy. The aim of this work was to assess the performance of a delivery system based on the original dendrimer. The dendrimer demonstrated low toxicity in mice (LD50 was 779 ± 111 mg/kg). To study the specificity of the dendrimer to tumor cells and its therapeutic efficacy, we used a nanostructure (NS) composed of the dendrimer itself, the RGD peptide and 188Re (188Re-NS). Lewis lung carcinoma LLC1 was used as a tumor model. The biodistribution analysis revealed that the compound effectively accumulated in the tumor demonstrating a tumor-to-normal ratio >1 (relative to healthy organs and tissues) and retention time of at least 6 hours. Injections of 185 MBq/kg 188Re-NS caused a statistically significant inhibition of tumor growth (p < 0.05) by day 7 following the injection (Т/С = 5%), which remained stable for 6 days. Our findings suggest that the proposed dendrimer is a promising platform for RP delivery.
VIEWS 54
Published online: 2018-12-31
DOI: 10.24075/brsmu.2018.088
Research into the molecular origin of surface-enhanced Raman spectra (SERS) of bacteria is a crucial step in assessing the future of SERS-based discrimination and identification of bacteria in clinical analysis, food quality control, etc. Previous studies have revealed that at 785 nm excitation wavelength SERS of bacterial cells placed on a solid surface functionalized with in-situ grown aggregated gold nanoparticles covered with SiO2 originate from a mixture of 6 purine derivatives (adenine, guanine, AMP, hypoxanthine, xanthine, and uric acid) that are released by the cells into the medium. The aim of the present work was to investigate whether such interpretation is possible with a different class of SERS substrates: silver nanoparticle sols at excitation wavelengths of 785 and 532 nm. The suspension of the Escherichia coli DH5α strain was used as a model bacterium. Sols of silver nanoparticles were obtained by reducing silver nitrate in the presence of alkaline hydroxylamine hydrochloride. Number-weighted mean hydrodynamic diameter of the particles was 43±2 nm. We confirm that at both excitation wavelengths the spectra can be best described as a superposition of 4 purine derivatives: adenine, guanine, hypoxanthine, and xanthine. Importantly, we have discovered that 1) the spectra of the purine mixture are characteristic of viable cells only; 2) due to the variations in the concentrations of purine metabolites released by the cells into the surrounding medium the spectra of a bacterial strain can vary significantly when a silver nanoparticle sol is used as a SERS substrate.
VIEWS 54