I am a scientist who works in Cancer Immunotherapy in Mainz, Germany.
University and Cell Medica
I studied Biochemistry and Immunology at Imperial College London from 2001 to 2005. I started working for a start up Biotech company called Cell Medica before the company even really existed. The CEO of the company had studied with me and picked out some people from the course to help him start his company. After the company started properly in February 2007 I started working in the lab, performing magnetic bead cell separations in a GMP clean room.
The goal was to pick out CMV specific T cells from leukapheresis donors, so that they can be infused into haematopoeitic stem cell transplant (HSCT) recipients. This is necessary as the immune system of someone who has received a HSCT is destroyed, so infections that lay dormant in the body, such as EBV, CMV and VZV, can start to expand without being controlled by the immune system. This is a big cause of morbity and mortality in HSCT recipients, that’s why there are anti-viral drugs used to treat the viral reactivations, but they are expensive and often need to be used repeatedly to tackle each reactivation, until the immune system recovers.
So I did the actual cell processing in a clean room, it was a little stressful at times, as everything has to be kept 100% sterile. Infecting an immune comprimised donor is not a good idea! As the company was small, I was a jack of all trades and also performed some of the immune monitoring, such as the flow cytometric analysis and ELISPOT assays, to show that the HSCT recipients immune system is recovering and that the transplanted CMV specific T cells are present and functional.
A new challenge
I did that until 2010 when I decided that I needed a new challenge. I couldn’t find anything in London, so decided I should spread my search area to include Western Europe too. After a false start with an application for a job in Switzerland (don’t ask), I found a job in Mainz, Germany for a company called Translational Oncology – TRON.
TRON Mainz – Cancer Immunotherapy
TRON is part of a complicated setup, now called the Mainz setting. There is the medical school, which is 100% research using lots of pre-clinical mouse models. Then there is TRON, which moves technology that looks promising towards the clinic. Then there is/was Biontech and Ganymed, two Biotech companies to want to commercialize therapies. When I started in 2010, everyone except for the Ganymed all sat together and worked together basically as if we were one big company. Since then the Biontech have built their own building and have moved in, meaning that TRON and the medical school are still largely working together, but Biontech is separate.
When I arrived in Germany, I didn’t speak any German. I had had a few lessons in my last few weeks in the UK, but I couldn’t really put sentences together or hold a conversation. Since then I’ve learned German and am pretty fluent now. I don’t ever need to speak English, though people do often like to speak English with me at work.
My role in TRON is quite different to what it was in Cell Medica. Here I perform the flow cytometric analysis for clinical studies. In the early years I was setting up and optimising the panels, along with picking markers and designing our peptide strategies. Now I perform intracellular cytokine secretion assays, antigen specific multimer stains, immunophenotyping, reference sample generation, DC generation and skin infiltrating lymphocyte culturing. These all fit into our wide array of clinical trials. The general theme of the trials that are being undertaken here in Mainz are using RNA vaccines to treat cancer. RNA can be targeted to APCs, so that they present specific epitopes. The expression is transient though, so it is not a gene therapy, meaning it is safe and not as heavily regulated as DNA based therapies. They also don’t need the cells to be proliferating to incorperate, meaning all antigen presenting cells and be targets for RNA therapies.
Collaboration with Biontech
The blockbuster for Biontech is the use of individualized RNA vaccines against cancer (IVAC). This could technically be used to treat anyone with cancer, regardless of cancer type. It also means that a vaccine made for one cancer patient is useless for another . It is truly an individualized (or personalized) therapy. Trials are ongoing, but the theory is sound and if the trial results are positive, then it could really be a game changer. Recently Genentech entered a collaboration with Biontech to move IVAC forward in combination with their checkpoint inhibitors. It will be interesting to see how things go moving forward.
Publications
I haven’t ever really been a publications person, as I have been doing clinical work. Here is my list of co-authorships anyway:
Nature. 2017 Jul 13;547(7662):222-226. doi: 10.1038/nature23003. Epub 2017 Jul 5.
Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer.
Sahin U, Derhovanessian E, Miller M, Kloke BP, Simon P, Löwer M, Bukur V, Tadmor AD, Luxemburger U, Schrörs B, Omokoko T, Vormehr M, Albrecht C, Paruzynski A, Kuhn AN, Buck J, Heesch S, Schreeb KH, Müller F, Ortseifer I, Vogler I, Godehardt E, Attig S, Rae R, Breitkreuz A, Tolliver C, Suchan M, Martic G, Hohberger A, Sorn P, Diekmann J, Ciesla J, Waksmann O, Brück AK, Witt M, Zillgen M, Rothermel A, Kasemann B, Langer D, Bolte S, Diken M, Kreiter S, Nemecek R, Gebhardt C, Grabbe S, Höller C, Utikal J, Huber C, Loquai C, Türeci Ö.
Nature. 2016 Jun 1;534(7607):396-401
Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy
Lena M. Kranz, Mustafa Diken, Heinrich Haas, Sebastian Kreiter, Carmen Loquai, Kerstin C. Reuter, Martin Meng, Daniel Fritz, Fulvia Vascotto, Hossam Hefesha, Christian Grunwitz, Mathias Vormehr, Yves Hüsemann, Abderraouf Selmi, Andreas N. Kuhn, Janina Buck, Evelyna Derhovanessian, Richard Rae, Sebastian Attig, Jan Diekmann, Robert A. Jabulowsky, Sandra Heesch, Jessica Hassel, Peter Langguth, Stephan Grabbe et al.
J Immunol Methods. 2018 Jul;458:74-82.
Bidmon N, Kind S, Welters MJP, Joseph-Pietras D, Laske K, Maurer D, Hadrup SR, Schreibelt G, Rae R, Sahin U, Gouttefangeas C, Britten CM, van der Burg SH.
J Immunol. 2015 Jun 15;194(12):6177-89
Generation of TCR-Engineered T Cells and Their Use To Control the Performance of T Cell Assays
Nicole Bidmon, Sebastian Attig, Richard Rae, Helene Schröder, Tana A. Omokoko, Petra Simon, Andreas N. Kuhn, Sebastian Kreiter, Ugur Sahin, Cécile Gouttefangeas, Sjoerd H. van der Burg and Cedrik M. Britten
Cancer Immunol Immunother. 2016 Oct;65(10):1277-87.
The right patient for the right therapy: 13th Annual Meeting of the Association for Cancer Immunotherapy (CIMT), Mainz, Germany, May 11-13, 2015.
Miller M, Jahndel V, Kutscher S, Mahr A, Rae R, Kloke BP
Cancer Immunol Immunother. 2015 Jul;64(7):923-30.
Cancer immunotherapy achieves breakthrough status: 12th annual meeting of the association for cancer immunotherapy (CIMT), Mainz, Germany, May 6-8, 2014.
Kloke BP, Mahr A, Jabulowsky RA, Kutscher S, Rae R, Britten CM.
Cancer Immunol Immunother. 2014 Jul;63(7):749-55. .
Toward the next waves of cancer immunotherapy: 11th Annual Meeting of the Association for Cancer Immunotherapy (CIMT), Mainz, Germany, May 14-16, 2013.
Kloke BP, Rae R, Mahr A, Burkhardt UE, Kvistborg P, Britten CM.
Cancer Immunol Immunother. 2013 May;62(5):975-81.
Toward next-generation cancer immunotherapy: 10th annual meeting of the Association for Cancer Immunotherapy (CIMT), Mainz, Germany, May 23-25, 2012.
Kloke BP, Kutscher S, Rae R, Kvistborg P, Britten CM, Hadrup SR.