0000000000177750
AUTHOR
Ulrich Luxemburger
showing 10 related works from this author
Abstract CT034: A first-in-human phase I/II clinical trial assessing novel mRNA-lipoplex nanoparticles for potent melanoma immunotherapy
2017
Abstract Therapeutic vaccination with tumor antigen-encoding RNAs by local administration is currently being successfully employed in various clinical trials. Advancing from local to more efficient systemic targeting of antigen-presenting cells (APCs), we have developed pioneering RNA-lipoplex (RNA(LIP)) immunotherapeutics for intravenous application based on the employment of well-known lipid carriers without the need for functionalization of particles with molecular ligands. The novel RNA(LIP) formulation has been engineered to preserve RNA integrity after intravenous injection and physicochemically optimized for efficient uptake and expression of the encoded antigen by APCs in various ly…
Humoral immune responses of lung cancer patients against the Transmembrane Phosphatase with TEnsin homology (TPTE).
2015
Abstract Objective The cancer/testis (C/T) antigen Transmembrane Phosphatase with TEnsin homology (TPTE) is aberrantly expressed in many tumors including lung cancer. In the present study, we analyzed TPTE-auto-antibodies in lung cancer patients. Methods Using a crude-lysate ELISA, we analyzed a large cohort of 307 sera from lung cancer patients and 47 healthy donors for TPTE-specific autoantibodies. Sero-reactivity was correlated with clinical parameters and patients’ survival. Results TPTE-specific antibodies were detected in 41 of 307 (13.4%) sera from lung cancer patients. Based on an optimal cut-off value calculated by ROC curve analysis sensitivity for diagnosing lung cancer was 52% a…
BNT162b2 induces SARS-CoV-2-neutralising antibodies and T cells in humans
2020
BNT162b2, a lipid nanoparticle (LNP) formulated nucleoside-modified messenger RNA (mRNA) encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) stabilized in the prefusion conformation, has demonstrated 95% efficacy to prevent coronavirus disease 2019 (COVID-19). Recently, we reported preliminary BNT162b2 safety and antibody response data from an ongoing placebo-controlled, observer-blinded phase 1/2 vaccine trial1. We present here antibody and T cell responses from a second, non-randomized open-label phase 1/2 trial in healthy adults, 19-55 years of age, after BNT162b2 prime/boost vaccination at 1 to 30 µg dose levels. BNT162b2 elicited strong antibody …
Abstract CT032: A first-in-human phase I/II clinical trial assessing novel mRNA-lipoplex nanoparticles for potent cancer immunotherapy in patients wi…
2016
Abstract Immunotherapeutic approaches have evolved as promising and valid alternatives to available conventional cancer treatments. Amongst others, vaccination with tumor antigen-encoding RNAs by local administration is currently successfully employed in various clinical trials. To allow for a more efficient targeting of antigen-presenting cells (APCs) and to overcome potential technical challenges associated with local administration, we have developed a novel RNA immunotherapeutic for systemic application based on a fixed set of four liposome complexed RNA drug products (RNA(LIP)), each encoding one shared melanoma-associated antigen. The novel RNA(LIP) formulation was engineered (i) to p…
Humoral immune responses of lung cancer patients against tumor antigen NY-ESO-1
2005
The cancer-associated antigen NY-ESO-1 is expressed in a number of malignancies of different histological type. Patients with NY-ESO-1 expressing tumors have been shown to bear circulating autoantibodies against this antigen. In this study, we have assessed the NY-ESO-I autoantibody response in patients with lung cancer by a serum ELISA. Using a serum dilution of 1:400 we detected seroreactivity in 35 of 175 (20%) of patients. Incidence of autoantibodies was significantly higher in patients suffering from non small cell lung cancer (NSCLC, 23%) as compared to those with small cell lung cancer (SCLC, 9%). In the NSCLC group, NY-ESO-I antibody was significantly more frequent in patients with …
Abstract CT156: A first-in-human phase I/II clinical trial assessing novel mRNA-lipoplex nanoparticles encoding shared tumor antigens for immunothera…
2018
Abstract Therapeutic vaccination with tumor antigen-encoding RNAs is being investigated in various clinical trials. Typically, the RNA vaccine is administered intradermally, subcutaneously or intranodally with the intention to get expression of the encoded antigens in local antigen-presenting cells (APCs). We have developed a novel class of RNA-lipoplex (RNA(LIP)) immunotherapeutics for intravenous application, which allow systemic targeting of APCs. RNA(LIP) is a novel nanoparticulate formulation of lipid-complexed mRNA which selectively delivers the functional mRNA to APCs in lymphoid compartments body-wide for efficient mRNA uptake and expression of the encoded antigen by APCs. Moreover,…
Abstract CT022: IVAC® MUTANOME - A first-in-human phase I clinical trial targeting individual mutant neoantigens for the treatment of melanoma
2016
Abstract One of the hallmarks of cancer is the inherent instability of the genome leading to multiple genomic alterations and epigenetic changes that ultimately drive carcinogenesis. These processes lead to a unique molecular profile of every given tumor and to substantial intratumoral heterogeneity of cancer tissues. Recently, a series of independent reports revealed that pre-formed neoantigen specific T-cell responses are of crucial relevance for the clinical efficacy of immune checkpoint inhibitors. However, spontaneous immune recognition of neoantigens seems to be a rare event with only less than 1% of mutations inducing a T-cell response in the tumor-bearing patient. Accordingly, only …
Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer
2017
T cells directed against mutant neo-epitopes drive cancer immunity. However, spontaneous immune recognition of mutations is inefficient. We recently introduced the concept of individualized mutanome vaccines and implemented an RNA-based poly-neo-epitope approach to mobilize immunity against a spectrum of cancer mutations. Here we report the first-in-human application of this concept in melanoma. We set up a process comprising comprehensive identification of individual mutations, computational prediction of neo-epitopes, and design and manufacturing of a vaccine unique for each patient. All patients developed T cell responses against multiple vaccine neo-epitopes at up to high single-digit p…
Abstract B041: A novel nanoparticular formulated tetravalent RNA cancer vaccine for treatment of patients with malignant melanoma
2016
Abstract Immunotherapeutic approaches have evolved as promising and valid alternatives to available conventional cancer treatments. Amongst others, vaccination with tumor antigen-encoding RNAs by local administration is currently successfully employed in various clinical trials. To allow for a more efficient targeting of antigen-presenting cells (APCs) we have developed a novel RNA immunotherapeutic for systemic application based on a fixed set of four liposome complexed RNA drug products (RNA(LIP)) each encoding one shared melanoma-associated antigen. Similar to other liposomal drugs, the four injectable RNA(LIP) products constituting the investigational medicinal product will be prepared …
Genomic response of the rat brain to global ischemia and reperfusion
2008
To identify genes that are involved in ischemia response of the brain, we have evaluated changes of gene expression in rat cerebrum after 15 min complete global ischemia, followed by reperfusion for 1 h, 6 h or 24 h. The expression profiles of approximately 30,000 transcripts from three subjects in each group (including sham-operated controls) were monitored employing oligonucleotide microarrays. About 20,000 transcripts were detectable in rat brains. The levels of 576 transcripts (approximately 2.9%) were significantly altered in response to experimental ischemia. 419 transcripts were up- and 157 downregulated; 39 transcripts changed after 1 h reperfusion, 174 after 6 h and 462 after 24 h.…