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Molecular Oncology & Immunology: Emile Voest

Emile Voest

Emile Voest, MD, Ph.D.Professor of Medical Oncology, Medical Director of the NKI

About Emile Voest

Emile Voest

 

Immunotherapy, genomics and (tumor)organoids

 

Immunotherapy

We recently published a very exciting translational study to generate better understanding of which tumors are recognized by T cells (Dijkstra et al. Cell, 2018). In this set of experiments we used autologous organoids to induce an immune response on PBMC. In colorectal cancer and NSCLC we have seen PBMC responses when exposed to autologous tumor organoids. These T cells can be expanded for further research and even in the future for T cell treatment. This creates a very interesting platform and studies are underway to better understand resistance to the immune system.

Several trials and translational studies are ongoing. The NICHE trial is a unique study that investigates the use of neoadjuvant immunotherapy in colorectal cancer. First results are now coming in which allows the assessment of safety and initial outcome. We also invested a great deal of time and energy in obtaining paired biopsies from melanoma or lung patients treated with immunotherapy. Large scale efforts to analyze WGS data of >100 patients treated with immunotherapy and for whom we have clinical outcome data are underway. These data are subsequently compared with the data set of paired biopsies of patients treated with immunotherapy. Furthermore, we have used computational biology to investigate the true value of mutual exclusivity (van der Haar et al. Cell, 2019).

Genomic guided personalized medicine

We have created a data base of almost 5000 patients with metastatic cancer (of any kind) underwent biopsies to obtain fresh tumor material at the start of new systemic treatment and were whole genome sequenced (WGS) in conjunction with clinical outcome data. The NKI alone has contributed >1000 patients to this unique Dutch data set. I am very excited that, in collaboration with HMF, in 2019 all patients of the NKI will have access to WGS, an unprecedented step in the implementation of precision medicine which will undoubtedly further our knowledge.

We continue the Drug Rediscovery Protocol, in short DRUP. In this multi-pharma (12 companies to date), multi-drug (26 drugs to date), multi-center (30 centers to date) study we now have created a platform through which patients can get access to approved medication based on a genomic profile coupled to a tumor type. These drugs are provided for free by pharma and the number of drugs and hospitals are expanding. In the first analysis we have encountered a clinical benefit ratio (defined as complete or partial remission or stable disease >16 weeks) of ~30%. This is surprisingly high and reflects that patient selection is key in such a personalized medicine approach.

Organoids as a tool to personalize medicine

Finally, in the context of our personalized medicine efforts we have investigated whether organoids derived from tumors from individual patients have the capacity to predict treatment responses. We have initiated several clinical trials to investigate the value of these organoids as predictive tools. These trials include validation studies in patients with chemotherapy and targeted therapy in lung and colorectal cancer (TUMOROID), organoid-guided experimental treatment studies (SENSOR) and more. We have now shown that tumor organoids can predict non-responsiveness to irinotecan-based chemotherapy but not to oxaliplatin-based treatment.

In summary, my group is strongly committed to develop a better understanding of individual tumors and their responsiveness to immunotherapy and targeted /chemotherapy. By combining basic research with translational studies we are  successful in bringing novel findings very quickly to patients.

Co-workers

Battaglia, Thomas

Thomas Battaglia

Ph.D. student

Experience

I received my BSc from New York University,where I performed research into the gut microbiome. I then obtained a MSc in Bioinformatics and Systems Biology (UvA-VU) in 2019 and subsequently join the groups of Emile Voest and Lodewyk Wessels as a PhD student.

My work focuses on leveraging large high-throughput sequencing projects to identify biomarkers related to patient response as well as explore the relationship between the microbiome and cancer. 

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Cattaneo

Chiara Maria Cattaneo MSc

Ph.D. student

Experience

After obtaining my Master of Science in "Molecular and Cellular Medical Biotechnology" at San Raffaele University in Milan, I started as a PhD student in the group of Emile Voest in May 2016.

My main project, in collaboration with another PhD student of our lab, is focused on the attempt to use patient-derived tumor organoids for immunotherapy. By investigating the organoids potential to evoke tumor-specific T cells responses, I hope not only to better understand what is driving (or inhibiting) these responses, but also to develop a new therapeutic  and personalized T cells "products".

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Dijkstra, Krijn

Krijn Dijkstra

Ph.D. student

Experience

I'm a PhD student in the group of Emile Voest. I received my training as a biomedical scientist and medical doctor in Utrecht, San Diego and Oxford. My project focuses on the potential of applying organoid technology to personalised cancer therapy. Specifically, we aim to predict therapy response and stratify patients to certain therapies based on drug screens in organoids. Second, we attempt to use organoids for immunotherapy by exploiting their potential to evoke tumor-specific T cell responses. The opportunity of working with this new model system and operating on the crossroads between the lab and the clinic makes this a very interesting and exciting project.

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Haar, van de Joris

Joris van de Haar MD MSc

Ph.D. student

Experience

I am a PhD student in the groups of Emile Voest and Lodewyk Wessels in the fields of bioinformatics and systems biology. I was trained as a medical doctor and biomedical scientist at the Utrecht University/Utrecht Medical Center and the University of California San Diego. I aim to combine biomedical and computational insights to realize personalized medicine. More specifically, I perform bioinformatics analyses on large patient-derived 'omic' datasets to understand why some patients respond to a specific therapy and others do not. In addition, I combine functional and computational approaches to map the molecular pathways that drive cancer.

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Hoes, Louisa

Louisa Hoes MD

Ph.D. student

Experience

After graduating as a medical doctor and working as an internist in training, I started as a PhD student in the group of Emile Voest in June 2017. My main project is coordinating the nationwide 'Drug-Rediscovery' trial (DRUP), in which patients are treated with targeted or immunotherapy, matched to their molecular tumor profile. We hereby aim to facilitate patient access to potentially effective, whilst creating a national platform in which targeted drugs and accompanying biomarkers can be tested across various tumor types. I'm also involved in clinical trials exploring the clinical applications of tumor
organoids.

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529318 S. Kaing

Sovann Kaing

Technician

Experience

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Ooft, Salo.jpg

Salo Ooft

Ph.D. student

Experience

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Luuk Schipper

Luuk Schipper

Ph.D. student

Experience

After a very brief period as a medical doctor on the wards of the Antoni van Leeuwenhoek, I started as a PhD student in the Voest group in April 2018. One of the pillars of the research group is to personalize cancer treatment. The emergence of organoids provides an interesting opportunity in this field. My efforts will mainly focus on the implementation of organoids in the clinical setting, hoping that patients will profit from the thrilling and exiting breakthroughs that have been and will be made in the lab.

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Stangl Christina

Christina Stangl MSc

Ph.D. student

Experience

I finished my Master Degree in Biology at the University of Regensburg, Germany. Thereafter I started a shared PhD project between the lab of Emile Voest at the NKI and Wigard Kloosterman at the UMC Utrecht.

The main focus of my PhD is to investigate the prevalence and role of gene fusions in the cancer genome. I am using the organoid system to characterize individual gene fusion. Furthermore, I want to evaluate the potential implications for personalized therapies.

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Vivien Veninga MSc

Ph.D. student

Experience

I studied Biochemistry at the Eberhard Karls University of Tübingen and the Ludwig Maximilian University of Munich in Germany. After obtaining my Master of Science I started as a PhD student in the lab of Emile Voest in June 2019.

Previously our group has established a co-culture system of patient derived tumor organoids and peripheral blood mononuclear cells to evaluate T cell response in the context of immunotherapy. My project will focus on expanding the co-culture system to other immune cells than T cells. This could potentially give us a better understanding of a broad spectrum of cancer immunotherapeutic approaches on a personalized level and a deeper insight into the crosstalk between immune cells.

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Wispelaere de, Wout

Wout de Wispelaere

Ph.D. student

Experience

After obtaining my Master of Bioscience Engineering in "Bio-nanotechnology" at KU Leuven, I started my PhD at KU Leuven at The Department of Gynecological Oncology. 

I am currently working as a guest researcher in the group of Prof. E. Voest, where we aim to establish patient-derived tumor organoids to unravel the resistance mechanisms to Pi3K/mTOR inhibition and PD-1 blockade in uterine leiomyosarcoma.

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Key publications View All Publications

  • Identifying Epistasis in Cancer Genomes: A Delicate Affair.

    Cell. 2019 May 30;177(6):1375-1383.

    van de Haar J, Canisius S, Yu MK, Voest EE, Wessels LFA, Ideker T.

    Link to Pubmed
  • Low and variable tumor reactivity of the intratumoral TCR repertoire in human cancers.

    Nat Med. 2019 Jan;25(1):89-94.

    Wouter Scheper, Sander Kelderman, Lorenzo Fanchi, Carsten Linnemann, Gavin Bendle, Marije de Rooij, Christian Hirt, Maarten Slagter, Krijn Dijkstra, Roel Kluin, Petur Snaebjornsson, Brad Nelson, Henry Zijlmans, Gemma Kenter, Emile Voest, John B.A.G. Haanen, and Ton N. Schumacher

    Link to Pubmed
 
 

Recent publications View All Publications

  • Phase Ib Study of Lumretuzumab Plus Cetuximab or Erlotinib in Solid Tumor Patients and Evaluation of HER3 and Heregulin as Potential Biomarkers of Clinical Activity.

    Clin Cancer Res. 2017 Sep 15;23(18):5406-5415.

    Meulendijks D, Jacob W, Voest EE, Mau-Sorensen M, Martinez-Garcia M, Taus A, Fleitas T, Cervantes A, Lolkema MP, Langenberg MHG, De Jonge MJ, Sleijfer S, Han JY, Calles A, Felip E, Kim SW, Schellens JHM, Wilson S, Thomas M, Ceppi M, Meneses-Lorente G, James I, Vega-Harring S, Dua R, Nguyen M, Steiner L, Adessi C, Michielin F, Bossenmaier B, Weisser M, Lassen UN.

    Link to Pubmed
  • A Systematic Analysis of Oncogenic Gene Fusions in Primary Colon Cancer.

    Cancer Res. 2017 Jul 15;77(14):3814-3822.

    Kloosterman WP, Coebergh van den Braak RRJ, Pieterse M, van Roosmalen MJ, Sieuwerts AM, Stangl C, Brunekreef R, Lalmahomed ZS, Ooft S, van Galen A, Smid M, Lefebvre A, Zwartkruis F, Martens JWM, Foekens JA, Biermann K, Koudijs MJ, Ijzermans JNM, Voest EE.

    Link to Pubmed
 

Contact

  • Office manager

    Alice Tondeur

  • E-mail

    a.tondeur@nki.nl

  • Telephone Number

    +31 (0)20 512 6930

2016-08-31 21.45.06
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