A5001240494- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Bacterial Infections and Vaccines
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Immunotherapy and Biomarkers
- Nanoparticle-Based Drug Delivery
- Toxin Mechanisms and Immunotoxins
- Immune Response and Inflammation
- Influenza Virus Research Studies
- Advanced Biosensing Techniques and Applications
- RNA Interference and Gene Delivery
- Herbal Medicine Research Studies
- Galectins and Cancer Biology
- Pharmacological Effects and Toxicity Studies
- Escherichia coli research studies
- Education, Psychology, and Social Research
- Microbial Inactivation Methods
- Pneumonia and Respiratory Infections
- Autophagy in Disease and Therapy
- Heat shock proteins research
- Endoplasmic Reticulum Stress and Disease
- Diabetes and associated disorders
Czech Academy of Sciences, Institute of Biotechnology
2022-2024
Johns Hopkins Medicine
2023-2024
Johns Hopkins University
2020-2024
University of Baltimore
2023
Czech Academy of Sciences, Institute of Microbiology
2012-2022
Czech Academy of Sciences
2009-2022
Czech Academy of Sciences, Institute of Macromolecular Chemistry
2007
IL-2 is potent imunostimulatory molecule that plays a key role in T and NK cell activation expansion. approved by the FDA to treat metastatic renal cancer melanoma, but its extremely short half-life serious toxicities are significant limitations of use. It was reported vivo biological activity can be increased association with anti-IL-2 mAb (S4B6). IL-2/S4B6 immunocomplexes were described highly stimulatory for memory CD8(+) cells intermediately also regulatory cells. IL-2/JES6-1 solely In...
Abstract IL-2 has been used to treat diseases ranging from cancer autoimmune disorders, but its concurrent immunostimulatory and immunosuppressive effects hinder efficacy. orchestrates immune cell function through activation of a high-affinity heterotrimeric receptor (composed IL-2Rα, IL-2Rβ, common γ [γc]). which is highly expressed on regulatory T (TReg) cells, regulates sensitivity. Previous studies have shown that complexation with the JES6-1 Ab preferentially biases cytokine activity...
Low-dose human interleukin-2 (hIL-2) treatment is used clinically to treat autoimmune disorders due the cytokine's preferential expansion of immunosuppressive regulatory T cells (Tregs). However, off-target immune cell activation and short serum half-life limit clinical potential IL-2 treatment. Recent work showed that complexes comprising hIL-2 anti-hIL-2 antibody F5111 overcome these limitations by preferentially stimulating Tregs over effector cells. Although promising, therapeutic...
The mechanisms of immunogenicity underlying mild heat-shock (mHS) treatment < 42°C tumor cells are largely attributed to the action proteins; however, little is known about undergoing severe cytotoxic (sHS > 43°C). Here, we found that sHS, but not mHS (42°C), induces immunogenic cell death in human cancer lines as defined by induction ER stress response and ROS generation, surface exposure calreticulin, HSP70 HSP90, decrease CD47, release ATP HMGB1. Only sHS-treated were efficiently killed...
Progress in cytokine engineering is driving therapeutic translation by overcoming these proteins' limitations as drugs. The interleukin-2 (IL-2) a promising immune stimulant for cancer treatment but limited its concurrent activation of both pro-inflammatory effector cells and anti-inflammatory regulatory T cells, toxicity at high doses, short serum half-life. One approach to improve the selectivity, safety, longevity IL-2 complexation with anti-IL-2 antibodies that bias towards cell...
High hydrostatic pressure (HHP) promotes key characteristics of immunogenic cell death (ICD), in thus far resembling chemotherapy and ionizing irradiation. Here, we demonstrate that cancer cells succumbing to HHP induce CD4+ CD8+ T cell-dependent protective immunity vivo. Moreover, show induction by relies on the overproduction reactive oxygen species (ROS), causing rapid establishment integrated stress response, eIF2α phosphorylation PERK, sequential caspase-2, -8 -3 activation....
ABSTRACT The adenylate cyclase toxin-hemolysin (CyaA, ACT, or AC-Hly) of Bordetella pertussis targets phagocytic cells expressing the complement receptor 3 (CR3, Mac-1, α M β 2 integrin, CD11b/CD18). CyaA delivers into an N-terminal adenylyl (AC) enzyme domain that is activated by cytosolic calmodulin and catalyzes unregulated conversion cellular ATP cyclic AMP (cAMP), a key second messenger subverting bactericidal activities phagocytes. In parallel, hemolysin (Hly) moiety forms...
Abstract The delicate balance of immune homeostasis is regulated by the interactions between cytokines and their cognate cell surface signaling receptors. There intensive interest in harnessing as drugs for diseases such cancer autoimmune disorders. However, multifarious often contradictory activities cytokines, coupled with short serum half-lives, limit clinical performance result dangerous toxicities. thus growing emphasis on manipulating natural to enhance selectivity, safety, durability...
Adenylate cyclase toxin (CyaA) is a key virulence factor of the whooping cough agent Bordetella pertussis. The targets CD11b-expressing phagocytes and delivers into their cytosol an adenylyl (AC) enzyme that subverts cellular signaling by increasing cAMP levels. In present study, we analyzed modulatory effects CyaA on adhesive, migratory antigen presenting properties Toll-like receptor (TLR)-activated murine human dendritic cells (DCs). enhanced TLR-induced dissolution cell adhesive contacts...
The Bordetella adenylate cyclase toxin-hemolysin (CyaA; also called ACT or AC-Hly) targets CD11b-expressing phagocytes and translocates into their cytosol an adenylyl (AC) that hijacks cellular signaling by conversion of ATP to cyclic AMP (cAMP). Intriguingly, insertion large passenger peptides removes the enzymatic activity but not cell-invasive capacity AC domain. This has repeatedly been exploited for delivery heterologous antigens cytosolic pathway dendritic cells CyaA/AC − toxoids, thus...
The adenylate cyclase toxin-hemolysin (CyaA) of Bordetella pertussis is a bi-functional leukotoxin. It penetrates myeloid phagocytes expressing the complement receptor 3 and delivers into their cytosol its N-terminal enzyme domain (~400 residues). In parallel, ~1300 residue-long RTX hemolysin moiety CyaA forms cation-selective pores permeabilizes target cell membrane for efflux cytosolic potassium ions. non-enzymatic CyaA-AC(-) toxoid, has repeatedly been successfully exploited as an antigen...
The adenylate cyclase (ACT) and the pertussis (PT) toxins of Bordetella exert potent immunomodulatory activities that synergize to suppress host defense in course whooping cough pathogenesis. We compared mouse lung infection capacities B . ( Bp ) mutants AC − or PT – producing enzymatically inactive toxoids confirm ACT action is required for maximal bacterial proliferation first days infection, whereas crucial persistence lungs. Despite accelerated near complete clearance from lungs by day...
SOT101 is a superagonist fusion protein of interleukin (IL)-15 and the IL-15 receptor α (IL-15Rα) sushi+ domain, representing promising clinical candidate for treatment cancer. among other immune cells specifically stimulates natural killer (NK) memory CD8 + T with no significant expansion or activation regulatory cell compartment. In this study, we showed that induced expression cytotoxic receptors NKp30, DNAM-1 NKG2D on human NK cells. stimulated dose-dependent proliferation relative both...
Interleukin-2 (IL-2) possesses a strong stimulatory activity for activated T and NK cells it is an attractive molecule immunotherapy. Nevertheless, extremely short half-life severe toxicities associated with high-dose IL-2 treatment are serious limiting drawbacks. In order to increase in vivo, we covalently conjugated synthetic semitelechelic polymeric carrier based on N-(2-hydroxypropyl)methacrylamide (HPMA) IL-2. Thus, synthesized IL-2-poly(HPMA) conjugate containing 2-3 polymer chains per...
Abstract BALB/c mice bearing syngeneic BCL1 leukemia, a mouse model of human chronic lymphocytic were treated with polymer-bound doxorubicin conjugate targeted BCL1-specific monoclonal antibody. Such treatment can cure up to 100% and the cured show long-lasting resistance leukemia. We that both CD4+ CD8+ T cells are required for establishment resistance, but only necessary its maintenance. express MHC class I II also costimulatory molecules CD80 CD86, which aid eliciting antitumor response....
We have investigated the effects of low-frequency pulsed electromagnetic field (LF-EMF) produced by BEMER device on experimental mouse T-cell lymphoma EL4 growing conventional and/or athymic (nude) mice. Exposure to EMF-BEMER slowed down growth tumor mass and prolonged survival animals. The effect was more pronounced in immuno-compromised nude mice compared ones. Acceleration never observed. No measurable levels Hsp 70 or increased specific anti-EL4 antibodies were detected serum taken from...
Progress in cytokine engineering is driving therapeutic translation by overcoming the inherent limitations of these proteins as drugs. The interleukin-2 (IL-2) harbors great promise an immune stimulant for cancer treatment. However, cytokine's concurrent activation both pro-inflammatory effector cells and anti-inflammatory regulatory T cells, its toxicity at high doses, short serum half-life have limited clinical application. One promising approach to improve selectivity, safety, longevity...