Imaging PD-L1 Expression with ImmunoPET
| Autor: | Anna Moroz, Khaled M. Jami, Chia Yin Lee, Hseuh Ling J. Oh, Emilie Jaumain, Cheng-I Wang, Yuqin S. Shen, Siok Ping Yeo, Victor Olivas, Albert J. Chang, Loc T. Huynh, Lawrence Fong, Michael J. Evans, Junnian Wei, Trever G. Bivona, Yung-hua Wang, Collin M. Blakely, Charles S. Craik, Matthew F.L. Parker, Charles Truillet, Benoit Jego, Natalia Sevillano |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Lung Neoplasms Immunoconjugates medicine.medical_treatment Pharmaceutical Science Inbred C57BL Epitope B7-H1 Antigen Prostate cancer Mice 0302 clinical medicine Cancer immunotherapy Carcinoma Non-Small-Cell Lung Positron Emission Tomography Computed Tomography Non-Small-Cell Lung Lung Cancer Tumor biology Chemistry Lung Cancer Recombinant Proteins 3. Good health 5.1 Pharmaceuticals 030220 oncology & carcinogenesis Biomedical Imaging Antibody Development of treatments and therapeutic interventions Biotechnology Biomedical Engineering Bioengineering Article Cell Line 03 medical and health sciences Medicinal and Biomolecular Chemistry Antigen Atezolizumab Cell Line Tumor medicine Animals Humans Lung cancer Pharmacology Radioisotopes Carcinoma Organic Chemistry medicine.disease Molecular biology Mice Inbred C57BL 030104 developmental biology Good Health and Well Being HEK293 Cells Cell culture Immunoglobulin G biology.protein Zirconium Biochemistry and Cell Biology |
| Zdroj: | Bioconjugate chemistry, vol 29, iss 1 Bioconjugate Chemistry Truillet, C; Oh, HLJ; Yeo, SP; Lee, C-Y; Huynh, LT; Wei, J; et al.(2018). Imaging PD-L1 Expression with ImmunoPET. BIOCONJUGATE CHEMISTRY, 29(1), 96-103. doi: 10.1021/acs.bioconjchem.7b00631. UCSF: Retrieved from: http://www.escholarship.org/uc/item/32z997tw |
| DOI: | 10.1021/acs.bioconjchem.7b00631. |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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