Press-room / Digest

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

DARPin_9-29-Targeted Gold Nanorods Selectively Suppress HER2-Positive Tumor Growth in Mice
A team of scientists from the Laboratory of molecular immunology of the IBCH RAS in collaboration with colleagues from Prokhorov General Physics Institute and Tel Aviv University developed innovative functional nano-biomaterials for selective photothermal therapy of HER2-positive breast cancers. It was demonstrated that gold nanorods (GNRs) stabilized with bovine serum albumin (BSA) and chemically conjugated to targeted vehicle specific to HER2 can be used for near infrared ablation of HER2-positive cancer in animal model. Stabilization of GNR with BSA leads to increase tumor uptake 16-fold in compare to naked GNR. As a result, photothermal therapy of HER2-positive tumor-bearing mice with HER2-specific BSA-stabilized GNRs leads to increase tumor growth inhibition coefficient in 2.5-fold compared to naked HER2-specific GNRs. Results are published in Cancers. Learn more

First crystal structure of bacterial oligopeptidase B in an intermediate state: the roles of the hinge region modification and spermine
Oligopeptidase B (OpB) is a two-domain serine peptidase with trypsin-like substrate specificity. OpB belongs to the prolyl oligopeptidase (POP) family and are found only in bacteria and protozoa. It is known that OpB are pathogenesis factors of protozoan infections and protect bacterial cells from a number of antimicrobial peptides. Nevertheless, they are the least studied representatives of POP, especially bacterial OpB, for which there was a complete lack of structural information. The researches from IBC RAS together with those of NRC Kurchatov Institute and the IBOC of the National Academy of Sciences of Belarus managed to obtain crystal structures of bacterial OpB from Serratia proteomaculans (PSP) with a modified hinge region. The work was published in the Biology journal. Learn more

Mambalgin-2 inhibits growth, migration, and invasion of metastatic melanoma cells by targeting the channels containing an asic1a subunit whose up-regulation correlates with poor survival prognosis
Melanoma is aggressive cancer characterized by acidification of extracellular environment. Scientists from the Laboratory of bioengineering of neuromodulators and neuroreceptors IBCh RAS together with colleages from NN Blokhin NMRCO showed for the first time that extracellular media acidification increases proliferation, migration, and invasion of patient-derived metastatic melanoma cells and up-regulates cell-surface expression of acid sensitive channels containing the ASIC1a, α-ENaC, and γ-ENaC subunits. No influence of media acidification on these processes was found in normal keratinocytes. This work was published in Biomedicines journal. Learn more

Pseudomonas phage MD8: genetic mosaicism and challenges of taxonomic classification of lambdoid bacteriophages
Fundamental questions of the evolution of viral genomes are the most important topic of virological research. As a result of the joint work of virologists from the Laboratory of Molecular Bioengineering of the IBCh RAS and the Limnological Institute of the RAS, a group of bacteriophages of the dangerous pathogen Pseudomonas was identified, the genomes of these bacterial viruses were studied, and it was shown that their formation was greatly influenced by multiple horizontal transfers, which led to pronounced genetic mosaicism. Scientists also put forward hypotheses about the origin of the new group and proposed basic principles for the taxonomic classification of lambdoid phages. The results are published in the International Journal of Molecular Sciences. Learn more