- CAR T-cell therapy against solid tumors and leukemias
- Enabling add-on-strategies for cellular therapies in solid tumors
- Antibody therapies against several cancer entities
- Influence of the cytokine Interleukin-22 on promoting tumor growth and metastases
Welcome to the homepage of the Kobold lab “immunopharmacology“!
The goal of our group is to contribute to preclinical development and advancement of novel drugs and immunotherapies against human’s biggest foe: cancer.
Research topics and goals
Within this raising field of immuno-oncology, we mainly focus on engineering of genetically modified T cells, with not only the famous Chimeric Antigen Receptor (CAR) T cells, but also own proprietary platforms, in several solid tumor type and leukemias. Within this field, we further develop approaches to enhance T cell´s full potential to approach and kill tumor cells via tumor infiltration and trafficking, T cell activation despite antigen escape and inhibition of local immunosuppression within the tumor microenvironment (TME) in vitro and in vivo. [Publications: 1, 2, 3, 4, 5, 6, 7]
In addition, we also examine how bi- and polyspecific antibodies may bring T cells in the proximity of tumor cells both for enhanced killing in vitro and survival in vivo [Publication: 8]. As the majority of these novel and uncharted approaches to attack solid tumors and leukemias are not approved the Food and Drug Administration (FDA) or the European Medicines Agency (EMA), our mission is clear: To Make That Happen.
Our group also investigates the interactions of tumor cells and the immune system within the tumor microenvironment (TME), especially at the level of cytokines secreted by tumor and immune cells. For example, we were able to identify the cytokine Interleukin-22 as a unique protein, as it is secreted by immune cells within the TME, but acts on its native Interleukin-22 receptor on tumor cells to promote cancer progression in several cancer models. In our work, we examine its detailed interaction partners and implications for immune cell exhaustion in vitro and in vivo [Publications: 9, 10].
As very little is known about its pro-tumoral and pro-metastastic characteristic,our mission is clear: To Shed Light On The Mechanisms Behind.
Challenges for CAR T-cell therapy in solid tumors
Prof. Dr. med. Sebastian Kobold
I studied medicine in Bordeaux, Homburg and Zurich and performed my doctoral thesis in the laboratory of C. Renner and A. Knuth in Zurich. After graduating from medical school, I started my residency in Hamburg and worked with D. Atanackovic in the field of tumor immunology. After a stay at Dana-Farber Cancer Institute, Boston, I established my own research group at the University hospital of the LMU. I am a board certified immunologist and clinical pharmacologist. Since 2019, I serve as Professor of Medicine and Experimental Immunooncology and as deputy director of the Division of Clinical Pharmacology at the University Hospital of the LMU. My research is focused on developing and testing novel strategies to treat cancer using the immune system. My goal is to bring these innovations to the clinics to the benefit of patients affected from cancer. Most of my free time is dedicated to my family and in what might be left of it, I run.
Dr. med. Sophia Stock
I studied Human Medicine at the Heidelberg University and Paris Descartes University. I performed my doctoral thesis in the laboratory of M. Schmitt in Heidelberg. After graduating from medical school, I started my residency in the hematology and oncology department at the University Hospital of the LMU Munich. I joined the working group of M. Subklewe in the field of translational cancer immunology. Since September 2020, I have been a fellow of the DKTK School of Oncology. Due to the support of the Else Kröner-Fresenius Clinician Scientist Program Cancer Immunotherapy and the Munich Clinician Scientist Program (MCSP) I have worked as a postdoctoral researcher in the working group of S. Kobold since April 2021. My ambition is to work as a Clinician Scientist specializing on immunotherapy. I spend most of my free time with my family and friends.
Dr. rer. nat. Donjete Simnica
I studied nutritional sciences in Hamburg and Munich. My master´s thesis, which I conducted in Cork/Ireland, focused on the interplay of immune cells and pain receptors in inflammatory bowel diseases. Back in Germany, I entered the field of immune receptor repertoires in the group of Prof. Dr. Mascha Binder where I also obtained my PhD in December 2020. Using high-throughput sequencing and bioinformatic methods we set out to find immune repertoire imprints that help to identify patients who benefit from immune therapies. My research in the group of Prof. Dr. Sebastian Kobold focuses on the identfication of tumor-specific targets and subsequent design and testing of novel immune cell therapies. Future goals include to learn more about our fascinating immune cells and use this knowledge to generate potent treatments from which hopefully many patients can benefit. In my free time I like to do yoga, go running and practice on my keyboard.
Dr. Iman Dalloul
I studied Biology and I completed my master’s degree in the field of immunotherapy in Lebanon. In 2014, I moved to France to do my PhD in the in the field of Immunogenetics in the CRIBL laboratory (Contrôle de la réponse Immune B et Lymphoproliférations) in Limoges under the supervision of Michel COGNÉ and Jeanne COOK-MOREAU. After my PhD, I worked for one year as a post-doctoral researcher in Bordeaux under the supervision of Maya SALEH in the ImmunoConcEpT laboratory (Immunology from Concept and Experiments to Translation). In 2022, I started a new post-doctoral position at the University Hospital of the LMU in the Division of Clinical Pharmacology. My research work aims to use the immune system in order to treat solid tumors. I like to spend my vacations travelling which allow me to learn and to discover new cultures and places.
I did my CTA education in Munich and started my first position at the GSF Munich GH (today: Helmholtz Zentrum). After my parental time I came back to University Hospital of the LMU. In the Division of Clinical Pharmacology at the University Hospital of the LMU I worked in different groups and since 2011 in the group of Prof. Dr. Sebastian Kobold. I have been responsible for a lot of different things, as e.g. for the organization of the relocation of the whole division to the Kubus 2015. Now, my primary responsibility is to manage the Kobold lab and to introduce all new members to their new working environment. My goal is to take care that we work in a nice and friendly atmosphere and help wherever I can. In my spare time I like to go hiking, skiing, sailing and traveling around the world with my family and friends. I try to ride my bike as often as I can.
Florian Märkl, M. Sc.
I studied molecular biotechnology and then biochemistry at the TUM in Munich. During my master studies I spent one semester abroad at the KTH in Stockholm and one semester as an intern at Roche in Penzberg. In 2019 I started my PhD in the research group of Prof. Dr. Sebastian Kobold at the University Hospital of the LMU working on T cell engineering for improving adoptive cell therapies in solid and liquid tumors. My goal is to advance immunotherapeutic strategies from testing them in preclinical models to clinical studies and ultimately to approved drugs. I spend most of my free time doing sports, cooking and meeting with friends.
Duc Huynh, M.Sc.
I did my undergraduate studies at the University of Missouri, Columbia in Biology. Afterwards, struck with a bit of wanderlust, I decided to pursue a Master’s degree at Kyoto University in Japan at the group of T. Fujita working on innate immunology. I’m now a PhD student in AG Kobold and my research interests are in dendritic cells, antigen presentation, and in developing therapeutic approaches combining innate and adaptive immunity to combat cancer.
Emanuele Carlini, M. Sc.
I graduated from King's College London with a Bachelor's in Pharmacology and from ETH Zurich with a Master's in Pharmaceutical Sciences. After conducting my Master Thesis at the University Hospital of Basel, focusing on immunology and cancer immunotherapy, I moved to Munich for my PhD studies.
At LMU, my work is concerned with investigating how to properly harness the function of cytokines to support and improve the efficacy of cellular therapies against cancer via the generation of chimeric cytokine receptors.
David Andreu Sanz, M. Sc.
I am a biotechnologist from Barcelona with a master’s in biomedical research. During my bachelor's studies, I had the chance to explore very different areas of research, including transcriptomics and embryology. During my master’s degree, I discovered my interest in cancer cell therapy and conducted my master thesis in Coquet lab at Karolinska Institutet in the field of tumor immunology. I am currently part of the Marie Skłodowska-Curie training network for Optimizing Adoptive T Cell Therapy of Cancer (T-OP) and my PhD project aims to improve CAR T cell functionality with cytokine signaling. In my free time I enjoy playing the piano and learning languages.
Dr. med. Sebastijan Spajic
I studied medicine in Zagreb and obtained my medical degree in 2019. During medical school I was working as a student assistant at the Department of Anatomy, Department of Internal Medicine and Department of Surgery. I performed my diploma thesis in the Laboratory for Stem Cells (Croatian Institute for Brain Research) under supervision of Prof. Mitrecic. After graduation I worked as a general physician. Driven by my interest in immuno-oncology I joined AG Kobold as a PhD student in 2021. My research is focused on improving CAR T cell therapy in solid tumors especially in colorectal carcinoma. My career goal is to be a physician scientist. In my free time I like long distance running and hiking.
I studied General Biology in my bachelor’s during which I investigated mechanisms of epigenetics and the methyltransferase Dnmt1 in the group of H. Leonhardt. Throughout my master’s degree in Human Biology at the LMU I focused on Immunology and Molecular Oncology, where I studied the combined therapeutic benefits of radio- and immunotherapy in cancer in the group of O. Boyman in Zürich, Switzerland. I started my PhD during fall 2021 in the Kobold Lab, where I now work on the development of cellular therapies for solid tumor entities. My free time I mostly spend with friends and family, I like travelling, eating, and enjoying life without a pipette in my hand!
doctoral researcher (MD track) (since 2019)
I am a 5th year MD student who has always been fascinated by the complex field of immunology and immunotherapy. After completing an undergraduate research program in this field, I am glad to be given the opportunity to work on my doctoral thesis in the Kobold lab. I am currently focusing on improving cellular immunotherapy by introducing novel immunomodulatory fusion proteins and enhancing trafficking of T cells into solid tumor tissue. If you don't see me around the lab, you might find me hiking in the mountains.
Öykü Umut, Ärztin
I studied medicine in Ankara at Hacettepe University and performed my doctoral thesis in our research group at LMU. My dissertation is about enhancement of CAR T cell therapy in solid tumors using chemokine receptors. I am currently wrapping up my thesis and intend to pursue my passion for oncology in the clinic. My hobbies include playing piano, jogging and swimming.
I did my Abitur in Bulgaria and started studying medicine in LMU Munich. I am doing my doctoral thesis in the research group of Kobold/Endres since 2021. My research is focused on improving the infiltration capacity of T-cells in tumor models. My goal is to finish medical school and combine clinical work with research, possibly both in the immunology field. In my free time I play basketball, go to the gym or go hiking.
Philipp Jie Müller
As I finished my high school diploma in Pforzheim in 2018, my dream came true to study medicine in Bavarian’s metropolitan area Munich. After the preclinical studies at the Luwig-Maximilians-University Munich and the first state examination in summer 2020, I continued the clinical part of my degree at the Technical University of Munich and the Klinikum rechts der Isar. At the DoktaMed 2020, I experienced the KlinPharm and the Kobold lab the first time, and was thrilled of their working spirit and future goals. Fortunately, my time within our group started in August 2021, as my first day was a pretty memorable hike from Schliersee to Tegernsee. To current state, I am working on the roles of cytokines in immune cell crosstalk and cancer progression, in particular the cytokine Interleukin-22 and its influence on metastases spreading. Besides, my work also includes doing immunofluorescence miscrocopy on human lung cancer tissues to ameliorate the understanding of Interleukin-22-secreting cells as well as their interaction partners. This brings me to my goals, to contribute to the everlasting work for improved understanting of cancer and its possible therapies. Concerning the future, it is my goal to further pursue research activities and at the same time clinical work with cancer patients on the university hospital level. After a hard lab day, I love to enjoy the best noodle place in Munich, the Max Beef Noodles Restaurant at the Sendlinger Tor. In addition, if I am not thinking of any lab work or clinical cases, I spent my leisure time pubquizzing with friends, biking in and around Munich, hiking in the alps and playing the guitar to four chord music hits.
Hi there, I am a 3rd year MD student at TU Munich currently working on my doctoral thesis at Prof. Kobold’s lab. In the group, I am working with special and newly designed CAR-T Cells to overcome the current hurdles of the tumor micro-environment in solid tumors. We try to enhance the migration of CAR-T Cells towards the tumor using in vitro and in vivo models. I will choose a medical profession where I can combine the aspects of research and patient treatment, but I don’t know exactly which one, yet. In my free time I like to connect, read, run and relax with friends in the Englischer Garten. I would rate my time at the lab 10/10.
I studied biology during my bachelor degree in La Rochelle and Bordeaux, in France. I then studied Cancer biology more specifically for my Masters in Bordeaux. I did my bachelor thesis in Newcastle, Australia, in the laboratory of Dr M. Dun, where I worked on treatment resistance in leukaemia. I am now doing my Masters thesis here, in the group of Professor S. Kobold, in collaboration with the laboratory of Professor F. Moreau-Gaudry in Bordeaux. I am focusing on pancreatic cancer and how to improve the infiltration of CAR-T cells into the tumor tissue using chemokine gradients, secreted by tumor cells. After my master's degree, I would like to continue my studies by doing a PhD in the field of immuno-oncology. In my free time, I really enjoy cooking and hiking.
I am currently pursuing my medical degree at the Ludwig Maximilian’s Universität in Munich (LMU), during which I have completed various internships in the department of internal medicine such as cardiology and emergency medicine, as well as a few semesters of work at the Division of Infectious Diseases and Tropical Medicine (LMU). With my doctoral thesis in the laboratory of the Clinical Pharmacology Department with AG Kobold/Endres (LMU) focusing on the immunotherapy of solid tumors, I hope to be able to contribute a little bit to the diverse field of possible novel treatments in oncology. Outside of university I can often be found in the mountains, either skiing, hiking or eating blueberries.
I did my Abitur in Munich and eventually started my medical studies at the LMU in 2018. During my preclinical studies I was able to participate in a research program, where I got the opportunity to get insight on experimental research and developed a big interest in that field. So I decided to do my doctoral thesis in the group of Kobold/ Endres. In the future I aim to become a clinician scientist to combine clinical work with experimental research. Whenever I got free time I either read, play the violin or do Karate.
I have been a medical student at LMU Munich since 2016 and completed my bachelor's degree in computer science at LMU in 2022. I am currently working on my doctoral thesis, a project on immunity after SARS-CoV-2 infection, which is a collaboration between the Department of Clinical Pharmacology, the Department of Infectious Diseases and the Institute of Tropical Medicine at the LMU. My aim here is to gain new insights into this infectious disease and the response of the immune system. In my spare time I am a member of a choir and play the guitar.
Top Ten Papers
Doctoral students as co-authors are underlined (starting in 1998)
1. Lesch S, Blumenberg V, Stoiber S, Gottschlich A, Ogonek J, Cadilha B, Dantes Z, Rataj F, Dorman K, Lutz J, Karches C, Heise C, Kurzay M, Larimer B, Grassmann S, Rapp M, Nottebrock A, Kruger S, Tokarew N, Metzger P, Hoerth Ch, Benmebarek MR, Dhoqina D, Gruenmeier R, Seifert M, Oener A, Umut Ö, . . . Rothenfusser S, Duewell P, Koenig L, Schnurr M, Subklewe M, Liss A, Halama N, Reichert M, Mempel T, Endres S, Kobold S.
T cells armed with C-X-C chemokine receptor type 6 enhance adoptive cell therapy for pancreatic tumours
Nature Biomedical Engineering 2021; 35:2243-2257.
2. Cadilha B, Benmebarek MR, Dorman K, Oener A, Lorenzini T, Obeck H, Väntinnen M, Di Pilato M, Pruessmann JN, Stoiber S, Huynh D, Maerkl F, Seifert M, Manske K, Suarez-Gosalvez J, Zeng Y, Lesch S, Karches CH, Heise C, Gottschlich A, Thomas M, Marr C, Zhang J, Pandey D, Feuchtinger T, Subklewe M, Mempel TR, Endres S, Kobold S.
Combined tumor-directed recruitment and protection from immune suppression enable CAR T cell efficacy in solid tumor.
Science Advances 2021; 7:eabi5781.
3. Benmebarek MR, Cadilha B, Hermman M, Lesch S, Schmitt S, Stoiber S, Darwich A, Augsberger Ch, Brauchle B, Rohrbacher L, Oener A, Seifert M, Schwerdtfeger M, Gottschlich A, Rataj F, Fenn NC, Klein Ch, Subklewe M, Endres S, Hopfner KP, Kobold S.
A modular and controllable T cell therapy platform for acute myeloid leukemia.
Leukemia 2021; 35:2243-2257.
4. Darwich A, Silvestri A, Benmebarek MR, Mouries J, Melacarne A, Cadilha B, Taleb A, Supino D, Obeck H, Sustmann C, Morelli L, Masci G, Losurdo A, Curigliano G, Kobold S, Penna G, Rescigno M.
Paralysis of the cytotoxic granule machinery is a new cancer immune evasion mechanism mediated by Chitinase 3-like-1.
Journal for Immunotherapy of Cancer 2021; 9:e003224.
5. Di Pilato M*, Kfuri-Rubens R*, Pruessmann J*, Ozga AJ*, Messemaker, M, Cadilha B, Sivakumar R, Cianciaruso Ch, Warner RD, Marangoni F, Carrizosa E, Lesch S, Billingsley J, Perez-Ramos D, Zavala F, Rheinbay E, Luster AD, Gerner MY, Kobold S, Pittet MJ, Mempel TR.
CXCR6 positions cytotoxic T cells to receive critical survival signals in the tumor microenvironment.
Cell 2021, 184:4512-30.
6. Liu X, Li J, Cadilha B, Markota A, Voigt C, Huang Z, Lin P, Wang D, Juncheng D, Kranz G, Krandick A, Libl D, Zitzelsberger H, Zagorski I, Braselmann H, Pan M, Zhu S, Huang Y, Niedermeyer S, Reichel Ch, Uhl B, Briukhovetska D, Suarez Gosalvez J, Kobold S, Gires O, Wang H.
Epithelial-type systemic breast carcinoma cells with a restricted mesenchymal transition are a major source of metastasis.
Science Advances 2019; 5:eaav4275.
10. Voigt C*, May P*, Gottschlich A*, Markota A, Wenk D, Gerlach I, Voigt S, Stathopoulos GT, Arendt K, Heise C, Rataj F, Janssen KP, Königshoff M, Winter H, Himsl I, Thasler W, Schnurr M, Rothenfußer S, Endres S, Kobold S.
Cancer cells induce interleukin-22 production from memory CD4+ T cells via interleukin-1 to promote tumor growth.
Proceedings of the National Academy of Sciences 2017; 10:1073
*contributed equally to this study
7. Kobold* S, Grassmann* S, Chaloupka M, Lampert C, Wenk S, Kraus F, Rapp M, Duewell P, Zeng Y, Schmollinger J, Schnurr M, Endres S#, Rothenfußer S#.
Impact of a new fusion receptor on PD-1-mediated immunosuppression in adoptive T cell therapy.
The Journal of the National Cancer Institute 2015; 107.
*contributed equally to this study, # share senior authorship
8. Kobold S, Steffen J, Chaloupka M, Grassmann S, Henkel J, Castoldi R, Zeng Y, Chmielewski M, Schmollinger J, Schnurr M, Rothenfußer S, Schendel DJ, Abken H, Sustmann C, Niederfellner CG, Klein C, Bourquin C, Endres S.
Selective bispecific T cell recruiting antibody enhances anti-tumor activity of adoptive T cell transfer. The Journal of the National Cancer Institute 2014; 107:364.
9. Kobold S, Völk S, Clauditz T, Küpper NJ, Minner S, Tufmann A, Düwell P, Lindner M, Koch I, Heidegger S, Merk M, Rothenfußer S, Schnurr M, Huber RM, Sauter G, Wilczak W, Endres S.
Interleukin-22 is frequently in lung cancer and may contribute to tumor progression in chemotherapy-resistant disease.
Journal of Thoracic Oncology 2013; 8:1032-1042.
Die Promotionssprechstunde findet jede Woche Montags zwischen 10 und 11 Uhr statt. Wir bitten um vorheriger Anmeldung unter:
Univ.-Prof. Dr. med. Sebastian Kobold bietet Studierenden der Medizin und Naturwissenschaftlicher Fächer eine persönliche Beratung rund um Fragen der Promotion zum Dr. med., Dr. hum. biol, Dr. rer. nat. oder PhD, insbesondere an der medizinischen Fakultät der LMU an. Ziel ist es über Chancen und Hürden der Promotion im Bezug auf die persönliche Situation zu informieren und zur Orientierung zu verhelfen.
We welcome unsolicited applications at all levels: for doctoral students of medicine and natural sciences, research assistant, technician and post-doctoral researcher. Please send your motivation letter, along with your CV and the contact of two references to: