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Tumor Immunology

Laboratory of Tumor Immunology
Tumors and T cell evasion - difficult to have one without the other

Understand how solid tumors evade immune control, and develop and explore therapies to (re-)establish tumor-specific responses of T lymphocytes

1. Development + testing of T cell receptor-engineered T cells
2. Understand + interfere with cross-talk between tumor cells and micro-milieu
3. Immune monitoring of T cell phenotype and function

Our contributions
• Developed molecularly enhanced T cell receptors (TCRs).
• Optimized and translated gene transfer and T cell processing methods into Good Clinical Practice (GCP)-compliant, clinical phase I/II protocols.
• Completed phase I/II study to assess the activity of (Chimeric Antigen Receptor) CAR-engineered T cells in advanced renal cell cancer, which was the first clinical study of its nature in Europe (P00.0040C, v14); and participate in multi-center phase II trials to assess the activity and optimized production protocols of NY-ESO1 TCR-engineered T cells in advanced esophago-gastric cancer and melanoma (EU FP7 studies).
• Initiated phase I/II study with MAGE-C2 TCRs in combination with strategies to enhance T cell co-stimulation in patients with metastatic melanoma and head-and-neck carcinoma; and NY-ESO1 TCRs in patients with various tumors (sponsored by Adaptimmune, Abingdon, UK).
• Monitor patient T cell phenotype and reactivity in multiple patient trials, amongst others: T cell therapy studies; vaccination studies; oncolytic adenovirus therapy; and graft predominance in double umbilical cord blood transplantations.

Reno groep 2016

Our Publications

Two key publications
Lamers CHJ, Sleijfer S, Vulto AG, Kruit WHJ, Kliffen M, Oosterwijk E, Debets R, Gratama JW, Stoter G. Treatment of metastatic renal cell carcinoma with autologous T-lymphocytes genetically retargeted against carbonic anhydrase IX: first clinical experience. J Clin Oncol, 2006 24:e20.
Straetemans T, Berrevoets C, Coccoris M, Treffers-Westerlaken E, Wijers R, Cole D, Dardalhon V, Sewell A, Taylor N, Verweij J, Debets R. Recurrence of melanoma following T cell treatment: continued antigen expression in a tumor that evades T cell recruitment. Mol Ther, 2015 23:396.

Two recent publications
Kunert A, van Steenbergen-Langeveld S, van Brakel M, da Silva M, Coulie P, Lamers C, Sleijfer S, Debets R. MAGE-C2 specific TCRs, in combination with epigenetic drug treatment of target cells, yield tumor-selective therapeutic T cells. J Immunol, 2016 197:2541.
Debets R, Donnadieu E, Chouaib S, Coukos G. TCR-engineered T cells to treat tumors: Seeing but not touching? Sem Immunol, 2016 28:10.