Özlem Türeci

Bio: Özlem Türeci is an academic researcher from University of Mainz. The author has contributed to research in topics: Cancer & Antigen. The author has an hindex of 56, co-authored 187 publications receiving 21168 citations. Previous affiliations of Özlem Türeci include Memorial Sloan Kettering Cancer Center & Ludwig Institute for Cancer Research.

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine.

Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a world...

Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates.

Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and the resulting disease, coronavirus disease 2019 (Covid-19), have spread to millions of persons worldw...

Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer

Abstract: 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 percentages. Vaccine-induced T cell infiltration and neo-epitope-specific killing of autologous tumour cells were shown in post-vaccination resected metastases from two patients. The cumulative rate of metastatic events was highly significantly reduced after the start of vaccination, resulting in a sustained progression-free survival. Two of the five patients with metastatic disease experienced vaccine-related objective responses. One of these patients had a late relapse owing to outgrowth of β2-microglobulin-deficient melanoma cells as an acquired resistance mechanism. A third patient developed a complete response to vaccination in combination with PD-1 blockade therapy. Our study demonstrates that individual mutations can be exploited, thereby opening a path to personalized immunotherapy for patients with cancer.

mRNA-based therapeutics — developing a new class of drugs

Abstract: In vitro transcribed (IVT) mRNA has recently come into focus as a potential new drug class to deliver genetic information. Such synthetic mRNA can be engineered to transiently express proteins by structurally resembling natural mRNA. Advances in addressing the inherent challenges of this drug class, particularly related to controlling the translational efficacy and immunogenicity of the IVTmRNA, provide the basis for a broad range of potential applications. mRNA-based cancer immunotherapies and infectious disease vaccines have entered clinical development. Meanwhile, emerging novel approaches include in vivo delivery of IVT mRNA to replace or supplement proteins, IVT mRNA-based generation of pluripotent stem cells and genome engineering using IVT mRNA-encoded designer nucleases. This Review provides a comprehensive overview of the current state of mRNA-based drug technologies and their applications, and discusses the key challenges and opportunities in developing these into a new class of drugs.

COVID-19 vaccine BNT162b1 elicits human antibody and T H 1 T cell responses.

Abstract: An effective vaccine is needed to halt the spread of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic. Recently, we reported safety, tolerability and antibody response data from an ongoing placebo-controlled, observer-blinded phase I/II coronavirus disease 2019 (COVID-19) vaccine trial with BNT162b1, a lipid nanoparticle-formulated nucleoside-modified mRNA that encodes the receptor binding domain (RBD) of the SARS-CoV-2 spike protein1. Here we present antibody and T cell responses after vaccination with BNT162b1 from a second, non-randomized open-label phase I/II trial in healthy adults, 18–55 years of age. Two doses of 1–50 μg of BNT162b1 elicited robust CD4+ and CD8+ T cell responses and strong antibody responses, with RBD-binding IgG concentrations clearly above those seen in serum from a cohort of individuals who had recovered from COVID-19. Geometric mean titres of SARS-CoV-2 serum-neutralizing antibodies on day 43 were 0.7-fold (1-μg dose) to 3.5-fold (50-μg dose) those of the recovered individuals. Immune sera broadly neutralized pseudoviruses with diverse SARS-CoV-2 spike variants. Most participants had T helper type 1 (TH1)-skewed T cell immune responses with RBD-specific CD8+ and CD4+ T cell expansion. Interferon-γ was produced by a large fraction of RBD-specific CD8+ and CD4+ T cells. The robust RBD-specific antibody, T cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest that it has the potential to protect against COVID-19 through multiple beneficial mechanisms. In a phase I/II dose-escalation clinical trial, the mRNA COVID-19 vaccine BNT162b1 elicits specific T cell and antibody responses that suggest it has protective potential.

Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine.

Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a world...

Cancer Genome Landscapes

Abstract: Over the past decade, comprehensive sequencing efforts have revealed the genomic landscapes of common forms of human cancer. For most cancer types, this landscape consists of a small number of “mountains” (genes altered in a high percentage of tumors) and a much larger number of “hills” (genes altered infrequently). To date, these studies have revealed ~140 genes that, when altered by intragenic mutations, can promote or “drive” tumorigenesis. A typical tumor contains two to eight of these “driver gene” mutations; the remaining mutations are passengers that confer no selective growth advantage. Driver genes can be classified into 12 signaling pathways that regulate three core cellular processes: cell fate, cell survival, and genome maintenance. A better understanding of these pathways is one of the most pressing needs in basic cancer research. Even now, however, our knowledge of cancer genomes is sufficient to guide the development of more effective approaches for reducing cancer morbidity and mortality.

Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer

Abstract: Immune checkpoint inhibitors, which unleash a patient’s own T cells to kill tumors, are revolutionizing cancer treatment. To unravel the genomic determinants of response to this therapy, we used whole-exome sequencing of non–small cell lung cancers treated with pembrolizumab, an antibody targeting programmed cell death-1 (PD-1). In two independent cohorts, higher nonsynonymous mutation burden in tumors was associated with improved objective response, durable clinical benefit, and progression-free survival. Efficacy also correlated with the molecular smoking signature, higher neoantigen burden, and DNA repair pathway mutations; each factor was also associated with mutation burden. In one responder, neoantigen-specific CD8+ T cell responses paralleled tumor regression, suggesting that anti–PD-1 therapy enhances neoantigen-specific T cell reactivity. Our results suggest that the genomic landscape of lung cancers shapes response to anti–PD-1 therapy.

Cancer Immunoediting: Integrating Immunity’s Roles in Cancer Suppression and Promotion

Abstract: Understanding how the immune system affects cancer development and progression has been one of the most challenging questions in immunology. Research over the past two decades has helped explain why the answer to this question has evaded us for so long. We now appreciate that the immune system plays a dual role in cancer: It can not only suppress tumor growth by destroying cancer cells or inhibiting their outgrowth but also promote tumor progression either by selecting for tumor cells that are more fit to survive in an immunocompetent host or by establishing conditions within the tumor microenvironment that facilitate tumor outgrowth. Here, we discuss a unifying conceptual framework called "cancer immunoediting," which integrates the immune system's dual host-protective and tumor-promoting roles.

Comprehensive molecular characterization of gastric adenocarcinoma

Abstract: Gastric cancer was the world’s third leading cause of cancer mortality in 2012, responsible for 723,000 deaths1. The vast majority of gastric cancers are adenocarcinomas, which can be further subdivided into intestinal and diffuse types according to the Lauren classification2. An alternative system, proposed by the World Health Organization, divides gastric cancer into papillary, tubular, mucinous (colloid) and poorly cohesive carcinomas3. These classification systems have little clinical utility, making the development of robust classifiers that can guide patient therapy an urgent priority. The majority of gastric cancers are associated with infectious agents, including the bacterium Helicobacter pylori4 and Epstein–Barr virus (EBV). The distribution of histological subtypes of gastric cancer and the frequencies of H. pylori and EBV associated gastric cancer vary across the globe5. A small minority of gastric cancer cases are associated with germline mutation in E-cadherin (CDH1)6 or mismatch repair genes7 (Lynch syndrome), whereas sporadic mismatch repair-deficient gastric cancers have epigenetic silencing of MLH1 in the context of a CpG island methylator phenotype (CIMP)8. Molecular profiling of gastric cancer has been performed using gene expression or DNA sequencing9–12, but has not led to a clear biologic classification scheme. The goals of this study by The Cancer Genome Atlas (TCGA) were to develop a robust molecular classification of gastric cancer and to identify dysregulated pathways and candidate drivers of distinct classes of gastric cancer.