Dendritic cell based cancer vaccine
Research Aim: Long term goal of the group of tumor immunotherapy is the development of dendritic cell based cancer vaccine. Administration of this vaccine should induce tumor cell-specific induce response and contribute to current treatment options.
This project was completed in March 2014, when two clinical studies aimed on treatment of prostate cancer and ovarian cancer were finished in University hospital Motol. Dendritic cell biology and their use in the immunotherapy of tumors have been studied at the Institute of Immunology for more than 10 years as documented by the list of publications. Further development and production of dendritic cells based vaccines was taken over by biotechnological company SOTIO.
Principal Investigators prof. Jiřina Bartůňková, M.D., Ph.D., MBA., Radek Špíšek, M.D., Ph.D.
Financial support: Research of dendritic cells at the Institute of Immunology, Charles University, 2nd Medical School has been supported by grants from Ministry of Education, grant agencies, grants form European Union
Dendritic cells in patients with diabetes mellitus type 1 and their high-risk relatives
The study is focused on denditic cells (DCs) in patients with DM type 1 and their high-risk relatives. We analyse numeber of DCs in peripheral blood and their cytokine profile after stimulation with ligands of Toll-like receptors.
Immunotherapy with dendritic cells based vaccines in patinets with ovarian carcinoma
Cytokine gene polymorphisms in children with sever form of atopic dermatitis (AD)
The aim of the study is to examine the genotype frequency of single nucleotide polymorphisms (SNPs) of twelve different cytokines in patients with severe form of AD and in healthy donors. Then we correlated the association between SNPs of interleukin (IL)-10 and occurrence of clinical and laboratory marks of inhalant allergy in AD patients. We did not found any differences in cytokine gene polymorphisms between patients anh healthy donors. Furthermore, we found statistical significance between the polymorphism of IL-10 and the appearance of allergic rhinitis in patients with severe form of AD.
Kinetics of dendritic cells reconstitution and costimulatory molecules expression after myeloablative allogeneic hematopoetic stem cell transplantation
Allogeneic hematopoetic stem cell transplantation (allo-HSCT) with myeloablative conditioning represents a unique opportunity to monitor the kinetics of reconstitution of hematopoetic cells. Aim of the study is to analyse the kinetics of DCs subsets reconstitution a costimulatory molecules expression after allo-HSCT.
The role of dendritic cells in allergic reaction: interaction between DC and allergens and development of allergic process
Allergic diseases are caused by immunopathologic reaction onto exogenous antigen – allergen. The allergic patients had connate predisposition to skew immune response to allergen to Th2 type. Dendritic cells (DCs) are professional antigen presenting cells which engulf, process and present antigens to T lymfocytes. In allergy, DCs stimule T lymphocytes to Th2 immune response and both amplify and maintain allergic inflammation. It is known fact that allergens are mostly glycoproteins, however the mechanisms of allergen binding to DC and its influence on phenotype and functionality of DC are not exactly examined. The aim of our study is to investigate direct effect of certain allergens on DC phenotype and function (mainly potential to polarize T lymphocyte differentiation). Simultaneously we are focusing on differencies of allergen effect on DCs between allergic and non-allergic pacients. Moreover, specific binding of allergen to the cell surface is still widely unknown and expected results would thus have great impact on the understanding of mechanisms of allergy. Allergic diseases are caused by immunopathologic reaction onto exogenous antigen – allergen. The allergic patients had connate predisposition to skew immune response to allergen to Th2 type. Dendritic cells (DCs) are professional antigen presenting cells which engulf, process and present antigens to T lymfocytes. In allergy, DCs stimule T lymphocytes to Th2 immune response and both amplify and maintain allergic inflammation. It is known fact that allergens are mostly glycoproteins, however the mechanisms of allergen binding to DC and its influence on phenotype and functionality of DC are not exactly examined. The aim of our study is to investigate direct effect of certain allergens on DC phenotype and function (mainly potential to polarize T lymphocyte differentiation). Simultaneously we are focusing on differencies of allergen effect on DCs between allergic and non-allergic pacients. Moreover, specific binding of allergen to the cell surface is still widely unknown and expected results would thus have great impact on the understanding of mechanisms of allergy.
The role of dendritic cell surface molecules in regulatory T cell induction
The project focuses on the study of correlation between phenotype characteristics of dendritic cells (DC) and their ability to induce regulatory T cells. We determine the expression of B7 family surface proteins, in detail we focus on PD-L1 and PD-L2 molecules.
Differences in tumor antigen presentation process in dendritic cells subpopulations
The project is focused on finding ways to accurately identify dendritic cells subpopulations in peripheral blood using multiparametric flow cytometry. These subpopulations will be sorted by flow sorter FACS Aria with an effort to reach the highest purity of the populations and viability of the cells. Using the confocal microscope we will observe the differences in tumor antigen presentation in the sorted dendritic cells subpopulations.
Examination of interaction of patients’ dendritic cells and lymphocytes with solid tumors of reproductive and urinary system
In following 3 years we aim to analyze the phenotype and function of T-lymphocytes and dendritic cells in the microenvironment of renal and ovarian cancer, compare them to peripheral blood of patients and healthy control. We further want to characterize the population of effector T-lymphocytes after the interaction with dendritic cells pulsed with the mixture of apoptotic tumor cells of prostate cancer cell lines.
Role of cytokine TSLP in immune system modulation and in pathogenesis of coeliac disease
Epithelial surface is imporant immune barrier, where first contacts of pathogens and host immune system take place. Cytokine TSLP (thymis stromal lymphopoetin) is recently discovered mediator of epithelial and dendritic cells communication. It influences stimulatory capacity dendritic cells and character of immune reaction (towards Th2 inflammatory type). In this project we would like to study communication between epithelial cells and dendritic cells and we are particularly interested in TSLP molecule and its influence on dendritic cells. Our hypothesis is that dendritic cells and gut epithelial cells crosstalk can also play important role in coeliac disease. We will study expression and function of TSLP in gut of patients with coeliac disease.
Influence of Toll-like receptor agonists on immunogenicity of tumour cells in B-chronic lymphocytic leukaemia
B-chronic lymphocytic leukemia (B-CLL) is most frequent leukemia in adult age incurable with conventional therapy. B-CLL tumour cells are weakly immunogenic which may contribute to disease progression and inhibit effective immunotherapy. Agents that enhance the immunogenicity of B-CLL cells may be useful in immunotherapeutic approaches to this disease. Non-malignant B cells express broad spectrum of Toll-like receptors, evolutionarily conserved proteins that recognize microbial molecules and initiate host defence. Some of their agonists allow improvement of their antigen-presentation functions. In this project we will study effect of known agonists of Toll-like receptors on B-CLL tumour cells. We will monitor activation status of B-CLL cells (signalling cascades activation, immunophenotype changes, cytokines, chemokines productions) and functional impact on T cell activation after treatment with TLR agonists in vitro. Furthermore, we will focus on detailed analysis of survival of the cells and influence of TLR triggering on apoptosis induction in relation to the disease prognosis.
The effect of calcitriol and calcitriol analog paricalcitol on dendritic cell function
We compare the effect of calcitriol and paricalcitol on functional characteristics of DC and on the following T cell induction
