A5079025879- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Chronic Lymphocytic Leukemia Research
- Radiopharmaceutical Chemistry and Applications
- HER2/EGFR in Cancer Research
- Lymphoma Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- Multiple Myeloma Research and Treatments
- Biosimilars and Bioanalytical Methods
- T-cell and B-cell Immunology
- Chronic Myeloid Leukemia Treatments
- Colorectal Cancer Treatments and Studies
- Glycosylation and Glycoproteins Research
- Acute Lymphoblastic Leukemia research
- Cerebrovascular and Carotid Artery Diseases
- Immune Cell Function and Interaction
- Pancreatic and Hepatic Oncology Research
- Virus-based gene therapy research
- Wnt/β-catenin signaling in development and cancer
- Oral and gingival health research
- Male Breast Health Studies
- vaccines and immunoinformatics approaches
- Lung Cancer Research Studies
Roche (Switzerland)
2022-2025
Karolinska Institutet
2011-2018
Karolinska University Hospital
2001-2015
University of Graz
2010
Sophiahemmet Hospital
2001-2007
Gene Therapy Laboratory
2002-2007
Background Many biomarkers have been proposed to be predictive of response anti-programmed cell death protein-1 (PD-1)/anti-programmed ligand-1 (PD-L1) checkpoint inhibitors (CPI). However, conflicting observations and lack consensus call for an assessment their clinical utility in a large data set. Using combined set trials real-world data, we assessed the prognostic outcome CPI non-small lung cancer (NSCLC). Methods Retrospective cohort study using 24,152 patients selected from 71,850 with...
Abstract Purpose: Previous studies have indicated that carcinoembryonic antigen (CEA) might be a suitable immunotherapeutic target in colorectal carcinoma (CRC). The aim of the present study was to analyze immunological and clinical effects vaccination with CEA together adjuvant granulocyte/macrophage colony-stimulating factor (GM-CSF). Experimental Design: Twenty-four resected CRC patients without macroscopic disease were immunized seven times recombinant at four different dose levels over...
Abstract Purpose: The immunocytokine cergutuzumab amunaleukin (CEA-IL2v) showed manageable safety and favorable pharmacodynamics in phase I/Ib trials patients with advanced/metastatic carcinoembryonic antigen-positive (CEA+) solid tumors, but this was accompanied by a high incidence of anti-drug antibodies (ADA). We examined B-cell depletion obinutuzumab as potential mitigation strategy. Experimental Design: Preclinical data comparing rituximab versus are summarized. Substudies investigated...
Abstract Purpose: Therapeutic depletion of immunosuppressive regulatory T cells (Tregs) may overcome resistance to cancer immunotherapies. RG6292 is an anti-CD25 antibody that preferentially depletes Tregs while preserving effector cell functions in preclinical models. The safety, pharmacokinetics, pharmacodynamics, and anti-tumor efficacy selective Treg by administered as monotherapy or combination with atezolizumab was evaluated two Phase I studies. Materials Methods: Adult patients...
<p><b>A,</b> Simulation plots: The PK/PD model was used to simulate both RG6292 and FOXP3<sup>+</sup> Treg levels following a range of doses. simulations were based on the population parameters from summarized (median) by analyte (green, non-Tregs; orange, Tregs) dose. solid lines represent median, shaded areas span 5th 95th percentiles, horizontal dashed 50% (red), 75% (magenta), 90% (blue) change baseline. <b>B,</b> Therapeutic window plot:...
<p>Representativeness of Study Participants.</p>
<p>Figure S1A. Study design - 1 (WP41188; NCT04158583). Figure S1B. 2 (BP42595; NCT04642365).</p>
<p>Figure S3. Spider plots showing percentage change from baseline in sum of diameters target lesions for efficacy-evaluable patients. (A) Study 1 (doses 18 mg and above) (B) 2 20 above).</p>
<p>Summary of key outcome parameters study 1 (WP41188; RG6292 every 3 weeks)</p>
<p>Figure S4. (A) The levels of peripheral CD8 T cells (CD45+CD3+CD8+) after treatment with RG6292 or (B) RG62962 in combination atezolizumab show less than 2-fold mean change absolute T-cell numbers intra patient variations (odds ratio CD8+ are calculated regards to CD3+ cells). (C) Quantitative analysis on-treatments biopsies matched baseline shows no systematic cells.</p>
<p>Safety summary</p>
<p>Summary of key outcome parameters study 2 (BP42595; RG6292 plus atezolizumab 1,200 mg every 3 weeks)</p>
<p>Patient disposition</p>
<p><b>A,</b> A single infusion of RG6292 results in sustained peripheral Treg depletion a dose-dependent manner and independent atezolizumab administration. <b>B,</b> leads to intratumoral reduction. The size the dots reflects number Tregs/mm<sup>2</sup> at baseline. Note that one sample cohort 7 (70 mg) had <1 Treg/mm<sup>2</sup> <b>C,</b> Change Teff/Treg ratio. Graphs show fold change from baseline ratio...
<p>Figure S2. Population PK/PD modeling approach: The model was used to simulate both RG6292 and FOXP3+ Treg levels, following a range of doses. which best describes the data is where previously defined drug levels (from PK model) stimulate loss CD25+ cells from plasma, in Michaelis-Menten manner. concentrations RG6282 cell count respective T were modeled simultaneous Proportional error for PD. utilized measured plasma different types, like or CD4+CD25+ IV infusion administration...
<div>AbstractPurpose:<p>Therapeutic depletion of immunosuppressive regulatory T cells (Treg) may overcome resistance to cancer immunotherapies. RG6292 is an anti-CD25 antibody that preferentially depletes Tregs while preserving effector T-cell functions in preclinical models. The safety, pharmacokinetics, pharmacodynamics, and antitumor efficacy selective Treg by administered as monotherapy or combination with atezolizumab were evaluated two phase I studies.</p>Patients...
Summary T‐cell immune dysfunction in patients with malignant tumours has been attributed to the altered expression of components receptor (TCR)/CD3 complex and their associated intracellular protein tyrosine kinases. In this study, four‐colour flow cytometry was applied study surface bound molecules TCR α β , CD28, CD152 CD154 involved signalling signal transduction CD3 ζ p56 lck p59 fyn ZAP‐70 phosphatidyl‐inositol‐3 kinase (PI3‐k) as well cytokines interferon‐ γ (IFN‐ ), interleukin (IL)‐4...
Abstract: Analysis of cytokine production is a tool to functionally characterise T cells. In this study, spontaneous and polyclonal activation induced in cells were assessed by flow cytometry patients with B‐CLL. Patients progressive disease had significantly increased number spontaneously producing IL‐2, IL‐4 GM‐CSF as compared healthy donors non‐progressive CLL, which was not the case for TNF‐α IFN‐γ However, no difference frequency these cytokines seen comparing control donors. Polyclonal...
Abstract The time kinetics of five cytokines [interleukin‐2 (IL‐2), IL‐5, interferon‐γ (IFN‐γ), granulocyte macrophage‐colony stimulating factor (GM‐CSF) and tumour necrosis factor‐α (TNF‐α)] one cytotoxic effector protein (granzyme B) was analysed by real‐time quantitative polymerase chain reaction (PCR) following in vitro stimulation human CD4 CD8 T lymphocytes. Two stimuli were used, a mitogen [phytohemagglutinin (PHA)] recall antigen [purified derivative (PPD)]. pattern cytokine mRNA...
Abstract Background: The fluorescence intensities of CD3, CD4 on T cells and CD20, CD22 molecules B were quantitatively measured lymphocytes from chronic lymphocytic leukemia (CLL) patients healthy donors. Methods: performance three different types microbeads was compared, i.e. Quantum equivalent soluble fluorochrome (Q‐MESF), simply cellular (QSC), QuantiBRITE™ (QB). As all PE‐conjugates had a F/P ratio 1:1, the MESF units represented also antibody binding capacity (ABC). Results: ABCs CD20...