A5002643568- CAR-T cell therapy research
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- Immune Cell Function and Interaction
- Cytomegalovirus and herpesvirus research
- Renal Transplantation Outcomes and Treatments
- Immunotherapy and Immune Responses
- Hematopoietic Stem Cell Transplantation
- Organ and Tissue Transplantation Research
- Silicon Carbide Semiconductor Technologies
- Chronic Lymphocytic Leukemia Research
- Nanowire Synthesis and Applications
- Organ Transplantation Techniques and Outcomes
- T-cell and B-cell Immunology
- HIV Research and Treatment
- vaccines and immunoinformatics approaches
- Histone Deacetylase Inhibitors Research
- Herpesvirus Infections and Treatments
- Biosimilars and Bioanalytical Methods
- Acute Lymphoblastic Leukemia research
- Advancements in Semiconductor Devices and Circuit Design
- Integrated Circuits and Semiconductor Failure Analysis
- Parvovirus B19 Infection Studies
University Hospital Heidelberg
2018-2024
Heidelberg University
2018-2024
Center for Rheumatology
2020
Despite encouraging results with chimeric antigen receptor T (CART) cells, outcome can still be improved by optimization of the CART cell generation process. The proportion less‐differentiated cells within transfused product is linked to enhanced in vivo expansion and long‐term persistence. clinically approved PI3Kδ inhibitor idelalisib well established treatment B malignancies. Besides pathway inhibition, modulate differentiation function. Here, detailed longitudinal analysis...
Abstract Chimeric antigen receptor T (CART) cells targeting CD19 have shown promising results in the treatment of chronic lymphocytic leukemia (CLL). However, efficacy seems to be inferior compared diffuse large B‐cell lymphoma or acute lymphoblastic leukemia. Impaired T‐cell fitness CLL patients may involved failure. Less‐differentiated naïve‐like play an important role CART expansion and long‐term persistence vivo. These are sparse patients. Therefore, optimization cell production...
Abstract Background Third-generation chimeric antigen receptor (CAR)-engineered T cells (CARTs) might improve clinical outcome of patients with B cell malignancies. This is the first report on a third-generation CART dose-escalating, phase-1/2 investigator-initiated trial treating adult refractory and/or relapsed (r/r) acute lymphoblastic leukemia (ALL). Methods Thirteen were treated escalating doses CD19-directed CARTs between 1 × 10 6 and 50 CARTs/m 2 . Leukapheresis, manufacturing...
Chimeric antigen receptor (CAR) T cells are considered genetically modified organisms (GMOs) and constitute gene therapy medicinal products. Thus, CAR cell manufacturing for clinical application is strictly regulated. Appropriate methods to assess vector copy numbers (VCNs) in products monitoring of frequencies patients required. Quantitative polymerase chain reaction (qPCR) the preferred method VCN assessment. However, no standardized procedure with high reproducibility has been described...
Chimeric antigen receptor (CAR) T cells spark hope for patients with CD19+ B cell neoplasia, including relapsed or refractory (r/r) acute lymphoblastic leukaemia (ALL) r/r non-Hodgkin's lymphoma (NHL). Published studies have mostly used second-generation CARs 4-1BB CD28 as costimulatory domains. Preclinical results of third-generation incorporating both elements shown superiority concerning longevity and proliferation. The University Hospital Heidelberg is the first institution to run an...
BACKGROUNDPreclinical experiments have shown that donor blood cells, modified in vitro by an alkylating agent (modified immune cells [MICs]), induced long-term specific immunosuppression against the allogeneic donor.METHODSIn this phase I trial, patients received either 1.5 × 106 MICs per kg BW on day -2 (n = 3, group A), or 108 B) -7 4, C) before living kidney transplantation addition to post-transplantation immunosuppression. The primary outcome measure was frequency of adverse events...
Chimeric antigen receptor (CAR) T cell therapy has shown promising responses in patients with refractory or relapsed aggressive B-cell malignancies that are resistant to conventional chemotherapy stem transplantation. A potentially combinatorial therapeutic strategy may be the inhibition of anti-apoptotic Bcl-2 family proteins, overexpressed most cancer cells. In this study we investigated combination 3rd-generation CD19.CAR-T cells and BH3 mimetics venetoclax, a inhibitor, S63845, Mcl-1...
Chimeric-antigen-receptor-T (CAR-T) cells are currently revolutionizing the field of cancer immunotherapy. Therefore, there is an urgent need for CAR-T cell monitoring by clinicians to assess expansion and persistence in patients. manufacturers researchers evaluate transduction efficiency vector copy number quality control. Here, CAR expression was analyzed peripheral blood samples from patients healthy donors flow cytometry with four commercially available detection reagents on gene level...
Graft-versus-host disease (GvHD), a severe complication of allogeneic hematopoietic stem cell transplantation, significantly affects the post-transplant morbidity and mortality. Systemic steroids remain gold standard for initial management GvHD. However, up to 60% patients will not sufficiently respond steroids. Extracorporeal photopheresis (ECP), cell-based immunotherapy, has shown good clinical results in such steroid-refractory/resistant GvHD patients. Given its immunomodulatory, but...
Abstract Third-generation chimeric antigen receptor T cells (CARTs) for relapsed or refractory (r/r) chronic lymphocytic leukemia (CLL) may improve efficacy compared to second-generation CARTs due their enhanced CAR design. We performed the first phase 1/2 investigator-initiated trial evaluating escalating doses of third-generation (HD-CAR-1) targeting CD19 in patients with r/r CLL and B-cell lymphoma. eligibility criteria were failure two therapy lines including at least one pathway...
CD56bri natural killer (NK) cells play an important role in the pathogenesis of graft-versus-host disease (GVHD) and immune defense early period after allogeneic hematopoietic stem cell transplantation. Extracorporeal photopheresis (ECP) as immunomodulating therapy has been widely used for GVHD treatment. However, mechanism action ECP still remains to be elucidated, particularly influence on NK cells. Thirty-four patients with steroid-refractory/resistant acute (aGVHD) ≥ °II moderate severe...
Chimeric antigen receptor (CAR) T cell (CART) therapy has been established as a treatment option for patients with CD19-positive lymphoid malignancies in both the refractory and relapsed setting. Displaying significant responses clinical trials, two second-generation CART products directed against CD19, axicabtagene ciloleucel (axi-cel) tisagenlecleucel (tisa-cel), have approved integrated into routine. However, experimental assay quantitative monitoring of these treated open domain are...
Chimeric antigen receptor T cell (CART) therapy is currently one of the most promising treatment approaches in cancer immunotherapy. However, immunosuppressive nature tumor microenvironment, particular increased reactive oxygen species (ROS) levels, provides considerable limitations. In this study, we aimed to exploit ROS levels microenvironment with prodrugs accelerators, which are specifically activated cells. Upon activation, accelerators induce further generation ROS. This leads an...
Chimeric antigen receptor T (CAR-T) cells targeting CD19 came into clinical practice for the treatment of B cell lymphoma in 2018. However, patients being treated often suffer from comorbidities such as chronic pain, cardiovascular diseases and arthritis. Thus, these frequently receive concomitant medications that include nonsteroidal anti-inflammatory drugs (NSAIDs) like cyclooxygenase (COX) inhibitors. Celecoxib, a selective COX-2 inhibitor, aspirin, non-selective COX-1 are used...
Chimeric-antigen-receptor (CAR)-T-cell therapy is already widely used to treat patients who are relapsed or refractory chemotherapy, antibodies, stem-cell transplantation. Multiple myeloma still constitutes an incurable disease. CAR-T-cell that targets BCMA (B-cell maturation antigen) currently revolutionizing the treatment of those patients. To monitor and improve outcomes, methods detect CAR-T cells in human peripheral blood highly desirable. In this study, three different detection...
The transcription factor SOX11 is a tumor-associated antigen with low expression in normal cells, but overexpression glioblastoma (GBM). So far, conventional surgery, chemotherapy, and radiotherapy have not substantially improved the dismal prognosis of relapsed/refractory GBM patients. Immunotherapy considered promising strategy against GBM, there fervent need for better immunotargets GBM. To this end, we performed an silico prediction study on SOX11, which primarily yielded ten...
Introduction: Cytomegalovirus (CMV) reactivation occurs in seronegative patients after solid organ transplantation (SOT) particularly from seropositive donors and can be lethal. Generation of CMV-specific T cells helps to prevent CMV reactivation. Therefore, we initiated a clinical phase I CMVpp65 peptide vaccination trial for end-stage renal disease waiting kidney transplantation. Methods: The highly immunogenic nonamer NLVPMVATV derived phosphoprotein 65(CMVpp65) water-in-oil emulsion...
The search for target antigens CAR-T cell therapy against multiple myeloma defined the B-cell maturation antigen (BCMA) as an interesting candidate. Several studies with BCMA-directed showed promising results. Second-generation point-of-care BCMA.CAR-T cells were manufactured to be of a GMP (good manufacturing practice) standard using CliniMACS Prodigy® device. Cytokine release in after stimulation BCMA positive versus negative lines, U266/HL60, was assessed via intracellular staining and...
Graft-versus-host disease (GVHD) occurs in about 10% to 33% of patients receiving "allogeneic" or "autologous" chimeric antigen receptor T (CAR-T) cells after preceding allogeneic hematopoietic stem cell transplantation (allo-HSCT) due the substantial presence alloreactive cells. Extracorporeal photopheresis (ECP) shows promising clinical outcomes treatment GVHD allo-HSCT without hampering antitumor and antiviral effects. This raises an interesting question: whether ECP might constitute a...
Significance Statement In previous work, the authors demonstrated that kidney transplant recipients developed donor-specific unresponsiveness when they were given a pretransplant infusion of modified donor-derived PBMCs. this study, provide evidence immunosuppressive properties these cells persist and is long-lasting. four patients who received highest dose immune cells, administration was associated with striking increase in IL-10–producing regulatory B lymphocytes consensus gene expression...
Chimeric antigen receptor (CAR) T cell therapy with axicabtagene ciloleucel, tisagenlecleucel and brexucabtagen ciloleucel has been adopted as the standard of care for patients refractory and/or relapsed CD19‑positive lymphoid malignancies. Monitoring kinetics CAR cells after administration is crucial patient follow‑up important to guide clinical decisions subjected therapy. Information transgene copies within a product prior administration, i.e. vector copy numbers, high importance warrant...