Imaging PD-L1 Expression with ImmunoPET.
Bioconjug Chem
; 29(1): 96-103, 2018 01 17.
Article
em En
| MEDLINE
| ID: mdl-29125731
ABSTRACT
High sensitivity imaging tools could provide a more holistic view of target antigen expression to improve the identification of patients who might benefit from cancer immunotherapy. We developed for immunoPET a novel recombinant human IgG1 (termed C4) that potently binds an extracellular epitope on human and mouse PD-L1 and radiolabeled the antibody with zirconium-89. Small animal PET/CT studies showed that 89Zr-C4 detected antigen levels on a patient derived xenograft (PDX) established from a non-small-cell lung cancer (NSCLC) patient before an 8-month response to anti-PD-1 and anti-CTLA4 therapy. Importantly, the concentration of antigen is beneath the detection limit of previously developed anti-PD-L1 radiotracers, including radiolabeled atezolizumab. We also show that 89Zr-C4 can specifically detect antigen in human NSCLC and prostate cancer models endogenously expressing a broad range of PD-L1. 89Zr-C4 detects mouse PD-L1 expression changes in immunocompetent mice, suggesting that endogenous PD-1/2 will not confound human imaging. Lastly, we found that 89Zr-C4 could detect acute changes in tumor expression of PD-L1 due to standard of care chemotherapies. In summary, we present evidence that low levels of PD-L1 in clinically relevant cancer models can be imaged with immunoPET using a novel recombinant human antibody.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Radioisótopos
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Zircônio
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Imunoglobulina G
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Carcinoma Pulmonar de Células não Pequenas
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Imunoconjugados
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Antígeno B7-H1
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Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
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Neoplasias Pulmonares
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article