A5101506108- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Photosynthetic Processes and Mechanisms
- Nanowire Synthesis and Applications
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Radioactive contamination and transfer
- Immune cells in cancer
- Antioxidant Activity and Oxidative Stress
- Advanced biosensing and bioanalysis techniques
- Multiple Sclerosis Research Studies
- Toxin Mechanisms and Immunotoxins
- Virus-based gene therapy research
- T-cell and B-cell Immunology
- vaccines and immunoinformatics approaches
- Advanced Biosensing Techniques and Applications
- Viral Infectious Diseases and Gene Expression in Insects
- Systemic Lupus Erythematosus Research
- Immune Response and Inflammation
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Algal biology and biofuel production
- SARS-CoV-2 and COVID-19 Research
- Ubiquitin and proteasome pathways
- Transgenic Plants and Applications
- Nicotinic Acetylcholine Receptors Study
Institute of Bioorganic Chemistry
2015-2024
Scripps Research Institute
2020-2024
Scripps (United States)
2024
Scripps Institution of Oceanography
2024
Ural State Agrarian University
2024
Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
2021-2022
Institute of Bioorganic Chemistry
2015-2021
Kazan Federal University
2015-2019
Russian Academy of Sciences
2015-2019
Institute of Chemical Biology and Fundamental Medicine
2017
Autoimmunity is intrinsically driven by memory T and B cell clones inappropriately targeted at self-antigens. Selective depletion or suppression of self-reactive cells remains a holy grail autoimmune therapy, but disease-associated receptors (TCRs) cognate antigenic epitopes remained elusive. A TRBV9-containing CD8+ TCR motif was recently associated with the pathogenesis ankylosing spondylitis, psoriatic arthritis acute anterior uveitis, HLA-B*27-presented were identified. Following...
Abstract COVID-19 pandemic caused by SARS-CoV-2 constitutes a global public health crisis with enormous economic consequences. Monoclonal antibodies against can provide an important treatment option to fight COVID-19, especially for the most vulnerable populations. In this work, potent binding Spike protein were identified from convalescent patients. Among them, P4A1 interacts directly and covers majority of Receptor Binding Motif Receptor-Binding Domain, shown high-resolution complex...
The 35-kDa Orange Carotenoid Protein (OCP) is responsible for photoprotection in cyanobacteria. It acts as a light intensity sensor and efficient quencher of phycobilisome excitation. Photoactivation triggers large-scale conformational rearrangements to convert OCP from the orange OCPO state red active signaling state, OCPR, demonstrated by various structural methods. Such imply complete, yet reversible separation domains translocation carotenoid. Recently, dynamic crystallography suggested...
Liver metastasis is the main cause of colorectal cancer (CRC)‐related death. Neutrophil extracellular traps (NETs) play important roles in CRC progression. Deoxyribonuclease I (DNase I) has been shown to alter NET function by cleaving DNA strands comprising backbone. Moreover, DNase displays high antimetastatic activity multiple tumor models. To circumvent long‐term daily administrations recombinant I, we have developed an adeno‐associated virus (AAV) gene therapy vector specifically express...
Chimeric antigen receptor (CAR) T cells targeting the CD19 are effective in treating adults and children with B-cell malignancies. Place-of-care manufacturing may improve performance accessibility by obviating need to cryopreserve transport centralized facilities. Here we develop an anti-CD19 CAR (CAR19) comprised of 4-1BB co-stimulatory TNFRSF19 transmembrane domains, showing anti-tumor efficacy vivo xenograft lymphoma model. CAR19 manufactured under current good practices (cGMP) at two...
The full potential of tumor-infiltrating lymphocyte (TIL) therapy has been hampered by the inadequate activation and low persistence TILs, as well inefficient neoantigen presentation tumors. We transformed tumor cells into artificial antigen-presenting (aAPCs) infecting them with a herpes simplex virus 1 (HSV-1)-based oncolytic encoding OX40L IL12 (OV-OX40L/IL12) to provide local signals for optimum T cell activation. infected displayed increased expression cell-related markers induced...
Tumor-derived extracellular vesicles (EVs) are active contributors in metastasis and immunosuppression tumor microenvironment. At least some of the EVs carry surface molecules such as tumor-associated antigens (TAAs) and/or checkpoint inhibitors, potentially could interact with T cells or CAR cells. Upon contact cells, alter their phenotype functions by triggering signaling through TCR reprogramming them to escape immune response. We hypothesize that possess TAA on will probably which can...
Here, we propose a possible photoactivation mechanism of 35-kDa blue light-triggered photoreceptor, the Orange Carotenoid Protein (OCP), suggesting that reaction involves transient formation protonated ketocarotenoid (oxocarbenium cation) state. Taking advantage engineering an OCP variant carrying Y201W mutation, which shows superior spectroscopic and structural properties, it is shown presence Trp201 augments impact one critical H-bond between protein. This confers unprecedented homogeneity...
Multiple sclerosis (MS) is a severe inflammatory and neurodegenerative disease with an autoimmune background. Despite the variety of therapeutics available against MS, development novel approaches to its treatment high importance in modern pharmaceutics. In this study, experimental encephalomyelitis (EAE) Dark Agouti rats has been treated immunodominant peptides myelin basic protein (MBP) encapsulated mannosylated small unilamellar vesicles. The results show that liposome-encapsulated...
Recent findings indicate that the ubiquitin-proteasome system is involved in pathogenesis of cancer as well autoimmune and several neurodegenerative diseases, thus a target for novel therapeutics. One disease related to aberrant protein degradation multiple sclerosis, an disorder involving processing presentation myelin autoantigens leads destruction axons. Here, we show brain-derived proteasomes from SJL mice with experimental encephalomyelitis (EAE) ubiquitin-independent manner generate...
CAR-T cell therapy is the most advanced way to treat resistant hematologic cancers, in particular B lymphomas and leukemias, with high efficiency. Donor T cells equipped ex vivo chimeric receptor recognize target tumor kill them using lytic granules. that CD19 marker of (CD19 CAR-T) are considered gold standard approved by FDA. But some cases, fails due immune suppressive microenvironment. It shown upregulate expression PD-L1 surface molecule binds increases level signal provided PD-1 on...
The development of chimeric antigen receptor (CAR) T cell therapy has become a critical milestone in modern oncotherapy. Despite the remarkable vitro effectiveness, problem safety and efficacy CAR against solid tumors is challenged by lack tumor-specific antigens required to avoid on-target off-tumor effects. Spatially separating cytotoxic function cells from tumor recognition provided protein mediators allows for precise control cytotoxicity. Here, high affinity capability bacterial...
Significance Neurotrophin receptors are a class of receptor tyrosine kinases that couple to signaling pathways critical for neuronal survival and growth. One member, TrkB, is particularly interesting because it plays role in many severe degenerative neurological diseases. The TrkB natural ligand brain-derived neurotrophic factor (BDNF) not suitable be developed as drug or therapy proved by previous unsuccessful clinical trials. Here we report selection method produced potent full agonist...
Abstract Ion channels play a central role in host of physiological and pathological processes are the second largest target for existing drugs. There is an increasing need reliable tools to detect visualize particular ion channels, but solutions suffer from number limitations such as high price, poor specificity, complicated protocols. As alternative, we produced recombinant chimeric constructs (FP-Tx) consisting fluorescent proteins (FP) fused with potassium channel toxins scorpion venom...
The heterogeneity of metabolic reactions leads to a non-uniform distribution temperature in different parts the living cell. demand study normal functioning and pathological abnormalities cellular processes requires development new visualization methods. Previously, we have shown that 35-kDa photoswitchable Orange Carotenoid Protein (OCP) has strong dependency photoconversion rates, its tertiary structure undergoes significant structural rearrangements upon photoactivation, which makes this...
Development of CAR-T therapy led to immediate success in the treatment B cell leukemia. Manufacturing therapy-competent functional cells needs robust protocols for ex vivo/in vitro expansion modified T-cells. This step is challenging, especially if non-viral low-efficiency delivery are used generate cells. Modern imperfect since non-specific stimulation results rapid outgrowth CAR-negative T cells, and removal feeder from mixed cultures necessitates additional purification steps. To develop...
B cells play an important role in the pathogenesis of both systemic and organ-specific autoimmune diseases. Autoreactive not only produce autoantibodies, but also are capable to efficiently present specific autoantigens T cells. Furthermore, can secrete proinflammatory cytokines amplify vicious process self-destruction. cell-directed therapy is a potentially approach for treatment various The depletion by anti-CD20/19 monoclonal antibody Retuximab® used diseases leads side effects should be...
We have previously shown that immunodominant MBP peptides encapsulated in mannosylated liposomes (Xemys) effectively suppressed experimental allergic encephalomyelitis (EAE). Within the frames of successfully completed phase I clinical trial, we investigated changes serum cytokine profile after Xemys administration MS patients. observed a statistically significant decrease MCP-1/CCL2, MIP-1 β /CCL4, IL-7, and IL-2 at time study completion. In contrast, levels TNF- α were remarkably elevated....
Comparative study of spectroscopic features reveals the structural determinants keto-carotenoids in photoactive water-soluble proteins.
After decades of nonspecific lymphoma therapy, personalized approaches such as described here are on the horizon.
This article offers a detailed review of the current approaches to anticancer therapy that target death receptors malignant cells. Here, we provide comprehensive overview structure and function their ligands, describe latest trends in development receptor agonists, perform comparative analysis. In addition, discuss DR4 DR5 agonistic antibodies are being evaluated at various stages clinical trials. Finally, conclude by stating agonists may be improved through increasing stability, solubility,...
The mechanisms triggering most of autoimmune diseases are still obscure. Autoreactive B cells play a crucial role in the development such pathologies and, particular, production autoantibodies different specificities. combination deep-sequencing technology with functional studies antibodies selected from highly representative immunoglobulin combinatorial libraries may provide unique information on specific features repertoires autoreactive cells. Here, we have analyzed cross-combinations...
Significance Developed quantum mechanics/molecular mechanics (QM/MM) supercomputation is used to identify maturation of immunoglobulin (Ig) reactivity through optimization amino acids in the catalytic core, focused on enhanced nucleophilic attack phosphorus. A computationally optimized variant, l -Leu47Lys, delivers 340-fold enhancement for paraoxon relative wild-type Ig-paraoxonase resulting from substrate-induced ionization Tyr37 nucleophile. Variant antibody stereoselectivity toward a...