BioNTech and collaboration partner TRON published promising results in “Nature”

First-ever clinical study demonstrates personalized RNA-based vaccine using mutant neo-epitopes as antigens activates immune system against individual mutations and exerts anti-cancer activity.

BioNTech AG, a fully-integrated biotechnology company pioneering individualized cancer immunotherapy, announced Phase I trial results demonstrating its IVAC® MUTANOME, an individualized RNA vaccine based on patient-specific mutations, induces strong immunogenicity as well as promising anti-tumor activity in high-risk patients with late-stage melanoma. Additionally, in this early trial, a majority of patients showed prolonged progression-free survival in comparison to historical controls. The first-in-human study applied a process covering the comprehensive identification of individual mutations from routine tumor biopsies to next generation sequencing, the computational prediction of potential neo-epitopes as vaccine targets, and the design and manufacturing of an RNA vaccine encoding multiple neo-epitopes unique for each patient. The data, published in Nature, were obtained from research conducted in collaboration with clinical partners and the translational research institute, TRON. These data are now available to APERIM consortium partners to further test developed software modules.

Press release
Nature Article – full text

 

“Austrian Platform for Precision Oncology” receives national funding

The Medical University of Innsbruck further expands its facilities for precision cancer.

The establishment of an accurate infrastructure for precision oncology is a major challenge for research organizations and clinics, as expertise and high-end equipment are required in various fields such as laboratory diagnostics, oncology, cellular and molecular biology as well as bioinformatics. Three Austrian medical universities in Innsbruck, Graz and Vienna have therefore bundled complementary expertise aiming to develop an Austrian platform for precision oncology.

The platform contains three components: (1) molecular characterization with next generation sequencing and T cell receptor sequencing, (2) cellular phenotyping for the determination of immune infiltrates, and (3) functional diagnostics with 3D cell culture and CRISP / Cas9 technology. “This nationwide initiative will accelerate the implementation of precision-oncology and enable the standardization of clinical procedures,” explains Zlatko Trajanoski, who is also responsible for this project, which is funded with 1.5 million € over a five-year period.

APERIM Partners present preliminary results at the annual meeting in Utrecht

The venerable University of Utrecht, in short distance to Amsterdam, was venue of the 2nd partner meeting of APERIM. From 3rd to 4th of April APERIM partners met to present and discuss first project results. In particular, developed software and databases to address specific challenges in the field of cancer immunology were presented. Regarding the planned objectives, good progress could be achieved. Various software prototypes have been developed and a number of web databases developed during the course of the project are now publicly accessible:

Data Integration and development of an advanced bioinformatic platform
The Cancer Immunome Atlas Database – TCIA was launched by the Medical University of Innsbruck. TCIA provides a comprehensive view of the cellular composition of the intratumoral immune infiltrates as well as cancer antigens of >8000 samples from The Cancer Genome Atlas (TCGA), which were analysed using state-of-the-art immunogenomic analytical pipelines.
Link: http://tcia.at

Automated quantification tool for tumor infiltrating lymphocytes (TILs) to stratify colorectal cancer patients
Partner Definiens developed the TIL analyser software as an image analysis solution to detect, quantify and evaluate tumour infiltrating lymphocytes in slide H&E images. This software is now tested and evaluated by APERIM partner data. INSERM in parallel is working the annotation of whole slide images in order to stratify CRC patients using immunoscore. Partner CNIC worked on the digital TIL sorter to quantify TILs from RNA-Seq data. A prototype software is established and will now be tested and evaluated, before it is integrated in TCIA bioinformatic platform.

Development of an analytical pipeline for NGS-guided personalised cancer vaccines
Three software parts will form this pipeline package. Partner TRON already successfully developed the iCaM2.0 NGSanalyser software, which is actually evaluated with clinical data. To predict which targets of the tumor surface will be immunogenic, University of Utrecht is working intensively on the second software, the immunopredictor with the planned delivery date in fall. As further important parts of the pipeline, University of Tübingen developed the EpitopeSelector as an open source software, further a novel approach to solve the subsequent problem of assembling the selected neo-epitopes into the final vaccine and a necessary framework to rapidly develop such advanced computational immunology approaches.

Links:
https://github.com/APERIM-EU/WP3-EpitopeSelector
ttps://github.com/FRED-2/OptiVac
https://github.com/FRED-2/fred2

The integration of all applications in one pipeline to identify optimal cancer vaccine targets will be reached by the end of the Project.

Predicting T-cell receptor (TCR) specifity for adoptive T-cell cancer therapy
Based on available NGS data Partner AptaIT generated a TCR Kit to analyse deriving TCR sequences. This software will now be tested and evaluated with further data. In order to develop a novel method to predict TCR specificity, Masaryk University built a database containing more than 5000 TCRs with known specificities, which can be now extended with additional datasets.
Link: https://vdjdb.cdr3.net/
Additionally, together with research results from University of Utrecht concerning epitope structures (pMHC), a TCR ontology database was generated.
Link: https://github.com/antigenomics/vdjdb-db
All tools together will finally help to describe TCR reactivity in human cancers.

In the remaining project year, Partners with access to clinical data will provide these data to test and evaluate the developed software modules and to fill open access databases. Preliminary results already show the high value and successful progress of the innovative APERIM bioinformatics platform.

Group picture Aperim

Partners of the H2020 project APERIM, coordinated by Univ.-Prof. Zlatko Trajanoski (front left) met in Utrecht to present and discuss preliminary project results.

 

 

Partner CNIC presents APERIM research in The New York Academy of Sciences

March 7th,
Last week The New York Academy of Sciences hosted the symposium “Quantitative Approaches in Immuno-Oncology”. Dr Carlos Torroja from Centro National de Investigationes Cardiovasculares Carlos III (CNIC) thereby presented first APERIM results in a much-noticed poster.
The symposium aimed to explore the promising field of immunotherapy in cancer treatment, covering the breadth of approaches needed to quantify interactions between tumors and the immune system. Quantitative Immuno-Oncology—sitting at the interface between immuno-oncology and quantitative approaches from mathematics, physics, and computer science—has emerged as a field that can significantly advance the ability to interpret existing large datasets, and perform predictive analyses.
In his poster Carlos Torroja presented first results of the APERIM project. The reserachers around Fátima Sánchez-Cabo (CNIC) and Zlatko Trajanoski from the Medical University of Innsbruck applied deep learning on a set of markers selected as very predictive of the amount of lymphocytes and tested it on the 1207 breast cancer samples from TCGA. The results agreed relatively well with the annotated amount of lymphocytes from TCGA and furthermore also the predicted survival time of the groups.

Download Poster


Image: © Fátima Sánchez-Cabo

Further Information:
Prof Dr Fátima Sánchez Cabo
Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid 28029, Spain
Fátima Sánchez Cabo: fscabo@cnic.es

Science-paper with Input of APERIM´s work group

Researchers from the Netherlands Cancer Institute and University of Oslo/Oslo University Hospital show that even if one’s own immune cells cannot recognize and fight their tumors, someone else’s immune cells might. Their proof of principle study was published in the journal Science on May 19th.

The published data show that adding mutated DNA from cancer cells into immune stimulating cells from healthy donors create an immune response by the healthy immune cells. By inserting the tumor cell recognition elements from the donor immune cells back into the immune cells of the cancer patients, the researchers were able to make cancer patients’ own immune cells recognize cancer cells.

The APERIM work group of the Netherlands Cancer Institute contributed with first project results to this remarkable study. Within APERIM, Ton Schumacher aims to further investigate the role of tumor-specific mutations and the resulting neo-antigens as targets for immunotherapy, both to be able to predict T-cell reactivity and to find ways to enhance neo-antigen specific T cell immunity in cancer patients.

Source:

Original paper:

Press release Euerkalert:

Contact:

Ton Schumacher
Senior Member NKI-AVL & Professor of Immunotechnology Leiden University
The Netherlands Cancer Institute
http://www.nki.nl/divisions/immunology/schumacher-t-group/
t.schumacher (at) nki.nl

Tumor instability and impact on patient survival: it all depends on the immune response.

Genetic and molecular characteristics are often used to classify tumors because stratification is the first step towards individualized cancer medicine with the aim to find the optimal treatment for each patient. In colorectal cancer for an example the diagnosis to have a genetic instable tumor indicates a favorable prognosis for the patient. Researchers from the Laboratory of Integrative Cancer Immunology led by Jérôme Galon (Inserm, Universités Pierre-

et-Marie-Curie et Paris Descartes, Cordeliers Research Center in Paris, France), in collaboration with MedImmune, the global biologics research and development arm of AstraZeneca, now could prove that the immunologic environment in and around colorectal cancer even plays a greater role to

stratify tumors than classification based on tumor (in)stability. These results could have important clinical implications for immunotherapy. The article detailing these results is published in the journal Immunity on March 15th 2016.

Press Release

 

Contact: Jérôme GALON

Laboratory of Integrative Cancer Immunology

INSERM UMRS1138, Cordeliers Research Center

15 rue de l’Ecole de Medecine, 75006, Paris, France

Email: jerome.galon@crc.jussieu.fr

 

Source: Integrative analyses of colorectal cancer show Immunoscore is a stronger predictor of patient survival than microsatellite instability, Immunity, 44, 1–14, March 15, 2016  Full text

1st Annual Meeting in Seefeld

Between Innsbruck and Munich Seefeld offers a beautiful landscape and renowned conference hotels, so the first annual partner meeting took place from March 9-10, 2016 in that inspiring surrounding area chaired by the coordinator Univ.-Prof. Dr Zlatko Trajanoski from the Medical University of Innsbruck. Representatives of all eleven partner institutes and companies met to exchange scientific results, control achievements and define next steps. Two members of the International scientific advisory board (ISAB), the ethical advisor as well as the EU project officer participated and further strengthened the progress of the project with their helpful recommendations.

APERIM_Team

Scientists of the University of Tübingen publish a framework to improve the design of novel cancer vaccines

Epitope-based vaccines has emerged as a promising approach to treat not only infectious diseases but also to promote the battle against cancer by a patient’s own immune system. Actually, the prediction and assembly of viable epitopes and spacers in a string-of-beads like polypeptide remain one of the challenges. The design of the spacers between the epitopes and order of the epitopes thereby seem to affect crucially the probability that the selected peptides will be fully recovered and subsequently presented by patient´s HLA molecules and that risk is reduced, that adverse neoepitopes are generated within this process.

Benjamin Schubert and Oliver Kohlbacher from the University of Tübingen proposed in their work, which recently was published in Genome Medicine, a mathematical model to design spacer sequences of optimal design. First results are promising, as they showed indeed higher recovery rates and lower neoepitope generation using the proposed framework.

Together with partners, the researchers of Tübingen are going to validate the model in experimental tests within the project APERIM. Results will show if this approach helps to improve and accelerate epitope vaccine development.

 

Schubert B, Kohlbacher O: Designing string-of-beads vaccines with optimal spacers, Genome Medicine 2016, 8:9  full text

Benjamin Schubert; Mathias Walzer; Hans-Philipp Brachvogel; Andras Szolek; Christopher Mohr; Oliver Kohlbacher: FRED 2 – An Immunoinformatics Framework for Python. Bioinformatics 2016; doi: 10.1093/bioinformatics/btw113  full text

 

Further information:
Benjamin Schubert
Eberhard Karls University Tübingen
Applied Bioinformatics Group
Sand 14, D-72076 Tübingen
schubert (at) informatik.uni-tuebingen.de

Kick-off Meeting in Mainz

Partner institutions of the APERIM project participated in the project kick off meeting on May 11th 2015 in Mainz. The meeting has been an excellent occasion to get to know all consortium members and to exchange in detail about the work packages and the next steps.

kickoff_aperim

 

Press Release

The Medical University of Innsbruck is coordinating the EU research project on personalised cancer immunotherapy

  • The “APERIM” project will start on 1 May: Precision medicine for cancer treatment
  • Cancer immunotherapy: Pioneering and targeted tumour treatment
  • Only EU project on personalised medicine coordinated in Austria

In future, cancer immunotherapy is to improve treatment of tumours. For this purpose, bioinformatics specialists at the Medical University of Innsbruck are developing a new treatment platform together with immunotherapy experts. The “APERIM” EU project is the only research project coordinated in Austria from the Horizon2020 Calls in the area of personalising health and care (H2020-PHC-2014).

Innsbruck 14/04/2015: On 1 May, the Medical University of Innsbruck will start an innovative research project to implement modern, personalised cancer immunotherapy: Univ.-Prof. Dipl.-Ing. Dr. Zlatko Trajanoski, Director of the Innsbruck Division of Bioinformatics, is coordinating the APERIM “Advanced bioinformatics platform for PERsonalised cancer IMmunotherapy” project. Eight academic partners and three companies are working on practical implementation of immunotherapy specifically for unique tumour mutations of individual patients. “We are creating the conditions needed to better treat cancer with state-of-the-art precision medicine in future,” explains Trajanoski, the project coordinator. “Many research papers have shown that cancer immunotherapy is suitable for successfully treating cancer.”

The researchers will receive three million euros in funding via the Horizon 2020 EU Grant Programme. Univ.-Prof Trajanoski from Innsbruck Biocenter is the only Austrian project coordinator in the “Personalising health and care” funding pool.

 

Immune system against cancer: Analysis of “next generation sequencing” data

The immune system protects the human body not only against foreign pathogens, but also against tumour cells. Cancer cells can escape the control of the immune system in various ways. However this reduced defensive reaction can be stimulated therapeutically, as numerous research papers have shown. The new findings and ways of obtaining more and more information from samples, known as “next generation sequencing” methods, require the development of new platforms to utilise the data to treat patients. Treatment platforms process the individual data of cancer patients to allow it to be used for therapy recommendations, for example. Bioinformatics methods permit the evaluation and processing of the specific information on the molecular fundamentals of individual tumours, which in turn forms the basis for personalised cancer immunotherapy.

 

“APERIM” – Four steps to personalised cancer immunotherapy

The “APERIM” project has four goals: A new database will store all molecular information on a tumour, a new analysis tool will permit quantification of tumour-infiltrated T cells, a software application will provide the information required to produce personalised, therapeutic vaccinations and a new method will be used to develop a special T cell gene therapy.

Univ.-Prof. Trajanoski and his colleagues plan to develop a database in which all information on a tumour – i.e. findings from the histopathological image analysis as well as genetic and clinical data – can be entered. That allows all molecular properties and specific mutations of a tumour to be stored and retreived. “This comprehensive information will then provide an important foundation for diagnosis and therapy,” explains Univ.-Prof Trajanoski, the project coordinator.

The second step will be the development of a tool for quantifying tumour-infiltrated T cells. “It is essential to determine the density and the subpopulations of the tumour-infiltrated T cells precisely to be able to identify high-risk patients. The more specific immune cells are infiltrating, the higher the chances of survival of cancer patients,” explains the expert.

The third project section will develop software to identify antigens for the development of individualised cancer vaccination based on the comprehensive detailed information. Every tumour has different properties, which makes it impossible to develop a single vaccination for a type of cancer. “Therapeutic vaccinations of this kind for treating cancer must be personalised and the software must facilitate the analysis required for this,” adds Trajanoski.

The fourth and last project target is a vision for the future in particular, as there have only been a few experimental studies to date. “We want to develop a new method which makes it possible to predict the antigen specificity and tumour activity of the T cells. Based on this information, individual T cell gene