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Sir Martin John Evans (English: Sir Martin John Evans, January 1, 1941 -) is a British scientist, one of the winners of the 2007 Nobel Prize in Physiology or Medicine, and a professor and president of Cardiff University.
马丁·约翰·埃文斯爵士(英语:Sir Martin John Evans,1941年1月1日-)是一位英国科学家,2007年诺贝尔生理学或医学奖获得者之一,英国卡迪夫大学教授、校长。
https://pubmed.ncbi.nlm.nih.gov/29125731/
https://pubmed.ncbi.nlm.nih.gov/30227708/
http://www.pubmedplus.cn/P/SearchQuickResult?wd=9445fcd4-4217-44f3-85a1-dfca2487eb78
Bioconjug Chem
. 2018 Jan 17;29(1):96-103.
doi: 10.1021/acs.bioconjchem.7b00631. Epub 2017 Nov 15.
Affiliations expand
PMID: 29125731
PMCID: PMC5773933
Free PMC article
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.
The authors declare the following competing financial interest(s): Michael J. Evans received consulting fees and owns shares in ORIC Pharmaceuticals, Inc. Michael J. Evans received research support from GE Healthcare.
Figure 1
Defining the optimal time after…
Figure 2
89 Zr-C4 detects PD-L1 expression…
Figure 3
89 Zr-C4 can specifically detect…
Figure 4
89 Zr-C4 can detect pharmacologically…
J Nucl Med. 2022 Aug;63(8):1259-1265. doi: 10.2967/jnumed.121.262967. Epub 2021 Dec 21.PMID: 34933891
Mol Pharm. 2019 Aug 5;16(8):3469-3476. doi: 10.1021/acs.molpharmaceut.9b00307. Epub 2019 Jul 8.PMID: 31283253
Mol Imaging. 2019 Jan-Dec;18:1536012119829986. doi: 10.1177/1536012119829986.PMID: 31044647 Free PMC article.
Cancer Biother Radiopharm. 2020 Oct;35(8):549-557. doi: 10.1089/cbr.2019.3056. Epub 2020 Apr 21.PMID: 32315549 Free PMC article.
Lung Cancer. 2017 Oct;112:200-215. doi: 10.1016/j.lungcan.2017.08.005. Epub 2017 Aug 10.PMID: 29191596 Review.
Imaging approaches and radiomics: toward a new era of ultraprecision radioimmunotherapy?
J Immunother Cancer. 2022 Jul;10(7):e004848. doi: 10.1136/jitc-2022-004848.PMID: 35793875 Free PMC article. Review.
Molecular imaging for cancer immunotherapy.
Immunooncol Technol. 2020 Mar 27;5:10-21. doi: 10.1016/j.iotech.2020.03.001. eCollection 2020 Mar.PMID: 35756142 Free PMC article. Review.
Development of Radiotracers for Imaging of the PD-1/PD-L1 Axis.
Pharmaceuticals (Basel). 2022 Jun 14;15(6):747. doi: 10.3390/ph15060747.PMID: 35745666 Free PMC article. Review.
EJNMMI Res. 2022 Jun 13;12(1):35. doi: 10.1186/s13550-022-00906-x.PMID: 35695985 Free PMC article.
Translating Molecules into Imaging-The Development of New PET Tracers for Patients with Melanoma.
Diagnostics (Basel). 2022 Apr 29;12(5):1116. doi: 10.3390/diagnostics12051116.PMID: 35626272 Free PMC article. Review.
Leach D. R.; Krummel M. F.; Allison J. P. (1996) Enhancement of antitumor immunity by CTLA-4 blockade. Science 271, 1734–6. 10.1126/science.271.5256.1734. - DOI - PubMed
Schumacher T. N.; Kesmir C.; van Buuren M. M. (2015) Biomarkers in cancer immunotherapy. Cancer Cell 27, 12–4. 10.1016/j.ccell.2014.12.004. - DOI - PubMed
Carbognin L.; Pilotto S.; Milella M.; Vaccaro V.; Brunelli M.; Calio A.; Cuppone F.; Sperduti I.; Giannarelli D.; Chilosi; et al. (2015) Differential Activity of Nivolumab, Pembrolizumab and MPDL3280A according to the Tumor Expression of Programmed Death-Ligand-1 (PD-L1): Sensitivity Analysis of Trials in Melanoma, Lung and Genitourinary Cancers. PLoS One 10, e0130142.10.1371/journal.pone.0130142. - DOI - PMC - PubMed
Patel S. P.; Kurzrock R. (2015) PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy. Mol. Cancer Ther. 14, 847–56. 10.1158/1535-7163.MCT-14-0983. - DOI - PubMed
Herbst R. S.; Soria J. C.; Kowanetz M.; Fine G. D.; Hamid O.; Gordon M. S.; Sosman J. A.; McDermott D. F.; Powderly J. D.; Gettinger S. N.; et al. (2014) Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515, 563–7. 10.1038/nature14011. - DOI - PMC - PubMed
Show all 23 references
Animals
B7-H1 Antigen / analysis*
Carcinoma, Non-Small-Cell Lung / diagnostic imaging*
Cell Line, Tumor
HEK293 Cells
Humans
Immunoconjugates / chemistry*
Immunoglobulin G / chemistry*
Lung / diagnostic imaging
Lung Neoplasms / diagnostic imaging*
Male
Mice
Mice, Inbred C57BL
Positron Emission Tomography Computed Tomography / methods*
Radioisotopes / chemistry*
Recombinant Proteins / chemistry
Zirconium / chemistry*
B7-H1 Antigen
CD274 protein, human
Immunoconjugates
Immunoglobulin G
Radioisotopes
Recombinant Proteins
Zirconium
Zirconium-89
Bioconjug Chem
. 2018 Oct 17;29(10):3476-3482.
doi: 10.1021/acs.bioconjchem.8b00632. Epub 2018 Sep 24.
Affiliations expand
PMID: 30227708
PMCID: PMC6430562
Free PMC article
The swell of experimental imaging technologies to noninvasively measure immune checkpoint protein expression presents the opportunity for rigorous comparative studies toward identifying a gold standard. 89Zr-atezolizumab is currently in man, and early data show tumor targeting but also abundant uptake in several normal tissues. Therefore, we conducted a reverse translational study both to understand if tumor to normal tissue ratios for 89Zr-atezolizumab could be improved and to make direct comparisons to 89Zr-C4, a radiotracer that we showed can detect a large dynamic range of tumor-associated PD-L1 expression. PET/CT and biodistribution studies in tumor bearing immunocompetent and nu/nu mice revealed that high specific activity 89Zr-atezolizumab (~2 μCi/μg) binds to PD-L1 on tumors but also results in very high uptake in many normal mouse tissues, as expected. Unexpectedly, 89Zr-atezolizumab uptake was generally higher in normal mouse tissues compared to 89Zr-C4 and lower in H1975, a tumor model with modest PD-L1 expression. Also unexpectedly, reducing the specific activity at least 15-fold suppressed 89Zr-atezo uptake in normal mouse tissues but increased tumor uptake to levels observed with high specific activity 89Zr-C4. In summary, these data reveal that low specific activity 89Zr-atezo may be necessary for accurately measuring PD-L1 in the tumor microenvironment, assuming a threshold can be identified that preferentially suppresses binding in normal tissues without reducing binding to tumors with abundant expression. Alternatively, high specific activity approaches like 89Zr-C4 PET may be simpler to implement clinically to measure the broad dynamic range of PD-L1 expression known to manifest among tumors.
The authors declare no competing interests.
Figure 1.. A summary of the biodistribution…
Figure 2.. Added atezo carrier redistributes 89…
Figure 3.. Added atezo carrier substantially elevates…
Mol Imaging Biol. 2020 Dec;22(6):1553-1561. doi: 10.1007/s11307-020-01527-3. Epub 2020 Aug 19.PMID: 32813112 Free PMC article.
Clin Cancer Res. 2020 Aug 1;26(15):3999-4009. doi: 10.1158/1078-0432.CCR-19-3137. Epub 2020 Jan 17.PMID: 31953313
Bioconjug Chem. 2019 May 15;30(5):1434-1441. doi: 10.1021/acs.bioconjchem.9b00178. Epub 2019 Apr 19.PMID: 30973703 Free PMC article.
J Nucl Med. 2022 Aug;63(8):1259-1265. doi: 10.2967/jnumed.121.262967. Epub 2021 Dec 21.PMID: 34933891
J Immunother Cancer. 2021 Jan;9(1):e002025. doi: 10.1136/jitc-2020-002025.PMID: 33483343 Free PMC article.
Chem Sci. 2022 May 6;13(21):6348-6354. doi: 10.1039/d2sc01887j. eCollection 2022 Jun 1.PMID: 35733897 Free PMC article.
Metal-mediated synthesis of pyrrolines.
RSC Adv. 2019 Feb 27;9(12):6804-6844. doi: 10.1039/c8ra10247c. eCollection 2019 Feb 22.PMID: 35518475 Free PMC article. Review.
Imaging immunity in patients with cancer using positron emission tomography.
NPJ Precis Oncol. 2022 Apr 7;6(1):24. doi: 10.1038/s41698-022-00263-x.PMID: 35393508 Free PMC article. Review.
Development and Validation of a PET/SPECT Radiopharmaceutical in Oncology.
Mol Imaging Biol. 2022 Feb;24(1):1-7. doi: 10.1007/s11307-021-01645-6. Epub 2021 Sep 20.PMID: 34542804 Free PMC article. Review.
Mol Imaging Biol. 2021 Dec;23(6):914-928. doi: 10.1007/s11307-021-01620-1. Epub 2021 Jul 6.PMID: 34231102 Free PMC article.
Animals
Antibodies, Monoclonal / chemistry
Antibodies, Monoclonal / pharmacokinetics
Antibodies, Monoclonal / therapeutic use*
Antibodies, Monoclonal, Humanized
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacokinetics
Antineoplastic Agents / therapeutic use*
Cell Line, Tumor
Drug Carriers
Drug Compounding
Drug Screening Assays, Antitumor
Humans
Mice
Mice, Nude
Positron Emission Tomography Computed Tomography
Radiopharmaceuticals / chemistry*
Radiopharmaceuticals / pharmacokinetics
Tissue Distribution
Zirconium / chemistry*
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antineoplastic Agents
Drug Carriers
Radiopharmaceuticals
atezolizumab
Zirconium
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