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Poster Display session

348 - PD-L1 microSPECT/CT imaging for longitudinal monitoring of PD-L1 expression in syngeneic and humanized mouse models for cancer

Date

14 Dec 2018

Session

Poster Display session

Presenters

Sandra Heskamp

Citation

Annals of Oncology (2018) 29 (suppl_10): x1-x10. 10.1093/annonc/mdy493

Authors

S. Heskamp1, S.R. Verhoeff2, P.J. Wierstra1, J.D.M. Molkenboer-Kuenen1, G.W. Sandker1, S. Thordardottir3, D. Olive4, J. Bussink5, O.C. Boerman1, H. Dolstra3, E.H.J.G. Aarntzen6, W.A. Hobo3

Author affiliations

  • 1 Radiology And Nuclear Medicine, Radboud university medical center, 6500HB - Nijmegen/NL
  • 2 Medical Oncology, Radboud University Medical Centre Nijmegen, 6525 GA - Nijmegen/NL
  • 3 Laboratory Of Hematology, Radboud university medical center, 6500HB - Nijmegen/NL
  • 4 Inserm U1068, Centre de Recherche en Cancérologie de Marseille (CRCM), 13288 - Marseille/FR
  • 5 Radiation Oncology, Radboud university medical center, 6500 HB - Nijmegen/NL
  • 6 Radiology And Nuclear Medicine, Radboud University Medical Centre Nijmegen, 6500 HB - Nijmegen/NL
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Resources

Abstract 348

Background

Antibodies that block the interaction between programmed death ligand 1 (PD-L1) and PD-1 have shown impressive responses in subgroups of cancer patient. PD-L1 expression in the tumor seems to be a pre-requisite for treatment response. However, it is heterogeneously expressed within tumor lesions and may change upon disease progression and treatment. Imaging of PD-L1 could aid in patient selection.

Methods

Previously, we showed the feasibility to image PD-L1 positive tumors in immunodeficient mice. However, PD-L1 is also expressed on immune cell subsets. Therefore, the aim of this study was to assess the potential of PD-L1 microSPECT/CT using radiolabeled anti-PD-L1 antibodies to 1) measure PD-L1 expression in two immunocompetent tumor models (syngeneic mice and humanized mice harboring PD-L1 expressing immune cells) and 2) monitor therapy induced changes in tumor PD-L1 expression levels.

Results

We showed that radiolabeled anti-PD-L1 antibodies accumulated preferentially in PD-L1 positive tumors, despite considerable uptake in certain normal lymphoid tissues (spleen and lymph nodes) and non-lymphoid tissues (duodenum and brown fat). Moreover, PD-L1 microSPECT/CT imaging could distinguish between high and low PD-L1 expressing tumors. Notably, presence of PD-L1 positive immune cells did not compromise tumor uptake of the anti-human PD-L1 antibodies in humanized mice. Most importantly, we demonstrated that radiotherapy induced up-regulation of PD-L1 expression in murine tumors which could be monitored with microSPECT/CT imaging.

Conclusions

Together, these data demonstrate that PD-L1 microSPECT/CT is a sensitive technique to detect varying levels of tumor PD-L1 expression and in the future, this technique may enable patient selection for PD-1/PD-L1 targeted therapy.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Radboud UMC.

Funding

Netherlands Organisation for Scientific Research and Dutch Cancer Society.

Disclosure

All authors have declared no conflicts of interest.

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