Tumor Immunology

About our research group

Research into interactions between tumor cells and their micro-environment, particularly immune cells, is critical to enhance our understanding of tumor evolution and therapy resistance, and to exploit this knowledge towards improved patient care.

Reno Debets’ laboratory (currently 15 people) has performed > 20 years of research in tumor immunity and T cell treatments, and has set up timely research lines and techniques to understand how solid tumors evade immune control, and develop and explore therapeutic strategies to (re)establish tumor-specific T cell responses.

Overall aim

Our aim is to define and understand shortcomings of T cell immunity in common tumor types and, together with selection and testing of antigen targets and T cell receptors (TCRs), enable treatment of patients with (combination) adoptive T cell therapy.

Our focus

• Develop and test adoptive T cell therapy: selection and validation of targets and receptors, gene-engineering of T cells, and implementation of clinical T cell treatments.
• Understand and intervene with T cell immunity: discovery and functional assessment of determinants of anti-tumor T cell immunity as well as intervention studies with (immune) modulators.
• Monitor patient T cell immunity: identification of T cell immunity in patients with various tumor types in relation to resistance to (immune)therapies; these patient immune-phenotypes will be used to stratify patients and guide selections of drugs that make tumors better amenable to T cell treatments.

• MC2 TCR T CELLS: a TCR to treat patients with MAGE-C2-positive melanoma and head and neck cancer using adoptive therapy with gene-engineered T cells.
• NEW TCR T CELLS: new roads to unique targets and pre-treatments for adoptive T cell therapy to treat common cancers.
• T CELL PROFILING: studying presence, localization of T cell subsets in hard-to-treat tumors.
• RESPONDER TRIAL: pembrolizumab treatment of metastatic urothelial cancers.

T-Cell Profiling

Our team is part of the laboratory of Tumor Immunology, Department of Medical Oncology, and interrogates T cell immunity in solid tumors

• Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience
• TCRs Genetically Linked to CD28 and CD3ε Do Not Mispair with Endogenous TCR Chains and Mediate Enhanced T Cell Persistence and Anti-Melanoma Activity
• Recurrence of melanoma following T cell treatment: continued antigen expression in a tumor that evades T cell recruitment
• T cell receptors for clinical therapy: in vitro assessment of toxicity risk
• Adoptive T Cell Therapy: New Avenues Leading to Safe Targets and Powerful Allies
• T cells lacking co-stimulatory receptors demonstrate enhanced frequency in NSCLC patients responding to nivolumab

Collaborations within Erasmus MC Cancer Institute:

• Dept of Neurology
• Dept of MDL
• Dept of Ear Nose & Troat (ENT)
• Dept of Urology
• Dept of Hematology

Collaborations outside Erasmus MC Cancer Institute:

• University of Lausanne: prof. dr. Georges Coukos
• University of Brussels: prof. dr. Pierre Coulie
• University of Berlin: prof. dr. Thomas Blankenstein
• Regensburg Center for Interventional Immunology: prof. dr. Hinrich Abken
• University of Pennsylvannia: prof. dr. Carl June

Related centers:

• Center for analysis of tumor micro-environment (Vectra 3.0; Emrah Balcioglu; part of our research group)
• Center for Cancer Computational Biology (Harmen van der Werken)
• Center for high-throughput drug screening (Opera Phoenix; Pim French)
• Center for gene-editing via CRISPR/CAS (Emma de Pater)
• Center for single cell isolation and analysis (VyCAP; Jaco Kraan)
• Center for applied molecular imaging (Monique Bernsen)
• ACE of Tumor Immunology and Immune Therapy (Reno Debets)
• ACE of Urogenital tumors (Chris Bangma)
• ACE of Immune diseases (Peter Katsikis)
• ACE of Organoids and Systems Biology (Luc van der Laan)
• ACE of Pharmacology and Therapeutics (Ron Mathijssen)

• European Community, 6th framework grant (018914); Adoptive engineered T-cell targeting to activate cancer killing ('ATTACK', 2006-2010). Coordinator: Hawkins B (Manchester, UK). Workpackage leader/PI: Debets R. 1,1 million €
• European Community, 6th framework grant (518234); Cancer Immuno Therapy ('CIT', 2006-2010). Coordinator: Boon T (Brussels, Belgium). Workpackage leader/PI: Debets R. 250 k€
• European Community, 7th framework ITN grant (R.238778.3); Advanced teaching and training for adoptive cell therapy (‘ATTRACT’, 2010-2013). Training coordinators: Gilham D (Manchester, UK), Debets R. 200 k€
• Dutch Cancer Society, EMCR 2011-5159; Good Manufacturing Practice (GMP) protocol to generate TCR-engineered T lymphocytes with a preferred in vitro phenotype and function in preparation of a clinical adoptive therapy trial to treat patients with MAGE-C2-positive tumors. PIs: Lamers C, Sleijfer S, Debets R. 180 k€
• Dutch Cancer Society; EMCR 2014-7087; Cranking up tumor-specific T cell responses in metastatic breast cancer. PI: Debets R; co-PI: Martens J: 460 k€
• Stop Hersentumoren, 2015. T cell therapy for low-grade gliomas. PI: French P; co-PIs: Debets R, Sillevis-Smitt P, Sleijfer S: 45 k€
• Dutch Cancer Society, EMCR 2015-7741; Adoptive therapy with T cells gene-engineered with a co-stimulatory TCR to treat patients with MAGE-C2-positive melanoma and head and neck cancer. PIs: Debets R, Lamers C, Sleijfer S. 570 k€
• Dutch Cancer Society, WUR 2015-7734; Food-derived β-glucans and fungal proteins to support anti-melanoma immune therapy. PI: Debets R; co-PIs: Govers C, Wichers H. 520 k€
• World Cancer Research, 2016; Harnessing miRNAs to restore CTL immunity to cancer. PI: Katsikis P; co-PIs: Erkeland S, Debets R. 50 k€
• Foundation for Liver and Gastrointestinal Research, 2016; Immune monitoring using PBMC from patients with PDAC. PI: Debets R; co-PIs: Lamers C, v Eijck C. 200 k€
• Erasmus MC Daniel den Hoed Foundation, 2017; Tumor Micro-Environment Screening Center. PI: Debets R. 600 k€
• Holland Health TKI, 2017; Towards dendritic cell immunotherapy as a maintenance treatment for patients with pancreatic cancer. PI: v Eijck C; co-PIs: Aerts J, Debets R together with Amphera. 50 k€
• Merck, 2017; Genomic and immune profiling of metastasized urothelial cancers. PI: Lolkema M; co-PIs: Debets R, de Wit R. 110 k€
• Dutch Cancer Society, EMC 2018-2/12033; Co-stimulatory T cell receptors to advance treatment efficacy of adoptively transferred T cells. PI: Debets R. 457 k€
• Stichting Zabawas/overleven met alvleesklierkanker, 2019; Meten en visualiseren van immuuncellen in alvleesklierkanker: ‘state-of-the-art’ techniek om therapiekeuze te verbeteren. PI: Debets R. 94 k€
• Erasmus MC Daniel den Hoed Foundation, 2019; Adoptive T cell therapy to treat common cancers: new roads to unique targets and pre-treatments. PI: Debets R. 500 k€
• NC3R, challenge 32 (transgene track), phase 1, 2019, Translatable multimodal imaging agent for tracking and quantifying cell therapies in vivo (CRACK-IT), Simon J. Srinivas M. Mondino A, Chaabane L, Debets R, Bernsen M, Maynard J: $100K.

Principal investigator: Reno Debets

Team members:

• Cor Lamers, assistant professor
• Emrah Balcioglu, postdoctoral fellow
• Vacancy, postdoctoral fellow
• Pim Mutsaers, onco-hematologist
• Dora Hammerl, PhD student
• Priscilla de Graaff, PhD student
• Maud Rijnders, PhD student
• Dian Kortleve, PhD student
• Shweta Mahajan, PhD student 
• Bas Weenink, PhD student 
• Chumut Phanthunane, PhD student 
• Cor Berrevoets, research technician C
• Mandy van Brakel, research technician B
• Rebecca Wijers, research technician B
• Astrid Oostvogels, research technician A 
• Alexandre Maraffa, Master student
• Collin Bakker, Bachelor student
• Rosita Pherai, secretary

Contact? Mail to secretary or PI.