Antibodies imaging for immune check point inhibitors

Our immune system is capable of recognizing and eliminating cancer cells. This process is tightly regulated by immune checkpoints and their ligands. A major inhibitory immune checkpoint is programmed death-1 (PD-1), which is expressed by T-cells. Its ligand PD-L1 is expressed by tumor cells and antigen presenting cells (APCs). By upregulating PD-L1, tumor cells inactivate T-cells and escape immune recognition and attack. Clinical trials with anti-PD-1/PD-L1 immune checkpoint inhibitors (ICI) have shown durable (≥ 1 year) antitumor activities in 15-20% of cancer patients. This shows that ICI significantly improve the outcome for a subgroup of patients. However, a large number of non-responding patients is unnecessarily exposed to an expensive, ineffective treatment and its associated side effects. To use these expensive drugs more effectively, there is an urgent need for a biomarker to accurately predict treatment response. Tumor that express high levels of PD-L1 and PD-1 are most likely to respond to ICI. Therefore, we develop novel radiotracers to non-invasively image tumor PD-1 and PD-L1 expression by PET and SPECT. Recently, we have shown that it is feasible to distuingish high, moderate, and low PD-L1 expressing tumors by SPECT/CT imaging, using radiolabeled anti-PD-L1 antibodies.

Figure 1. SPECT/CT scans of mice bearing subcutaneous human breast cancer xenografts, with different PD-L1 expression levels, on both flanks (indicated with the white arrows). Tumor cross sections as measured with SPECT, ex vivo autoradiography and PD-L1 immunohistochemistry (IHC).

Collaborations

  • Willemijn Hobo
  • Harry Dolstra
  • Laboratory Medicine – Laboratory of Hematology, Radboud University Medical Center, Nijmegen, The Netherlands

People

Publications

  • S. Lütje, S. Heskamp, A.S. Cornelissen, T.D. Poeppel, S.A. van den Broek, S. Rosenbaum-Krumme, A. Bockisch, M. Gotthardt, M. Rijpkema and O.C. Boerman. "PSMA Ligands for Radionuclide Imaging and Therapy of Prostate Cancer: Clinical Status", Theranostics 2015;5(12):1388.

  • S. Heskamp, W. Hobo, J.D. Molkenboer-Kuenen, D. Olive, W.J.G. Oyen, H. Dolstra and O.C. Boerman. "Non-invasive imaging of tumor PD-L1 expression using radiolabeled anti-PD-L1 antibodies", Cancer Research 2015;75:2928-2936. Abstract/PDF DOI PMID

  • K. Aben, S. Heskamp, M. Janssen-Heijnen, E. Koldewijn, C. van Herpen, L. Kiemeney, E. Oosterwijk and D.J. van Spronsen. "Better survival in patients with metastasised kidney cancer after nephrectomy: a population-based study in the Netherlands", European Journal of Cancer 2011;47(13):2023-2032.

  • M.J. Coenen, G. Trynka, S. Heskamp, B. Franke, C.C. van Diemen, J. Smolonska, M. van Leeuwen, E. Brouwer, M.H. Boezen, D.S. Postma and others. "Common and different genetic background for rheumatoid arthritis and coeliac disease", Human molecular genetics 2009;18(21):4195-4203.