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诺奖文集 2007年诺贝尔医学奖 埃文斯 英国科学家

已有 880 次阅读 2022-9-14 06:47 |个人分类:诺贝尔奖|系统分类:教学心得


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://baike.baidu.com/item/%E9%A9%AC%E4%B8%81%C2%B7%E7%BA%A6%E7%BF%B0%C2%B7%E5%9F%83%E6%96%87%E6%96%AF/10786494?fromModule=lemma_inlink&fromtitle=%E9%A9%AC%E4%B8%81%C2%B7%E5%9F%83%E6%96%87%E6%96%AF&fromid=8252237


https://pubmed.ncbi.nlm.nih.gov/29125731/


https://pubmed.ncbi.nlm.nih.gov/30227708/


summary-EvansMJ-set.txt


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.

Imaging PD-L1 Expression with ImmunoPET

Charles Truillet 1 2Hsueh Ling J Oh 3Siok Ping Yeo 3Chia-Yin Lee 3Loc T Huynh 1Junnian Wei 1Matthew F L Parker 1Collin BlakelyNatalia SevillanoYung-Hua Wang 1Yuqin S Shen 1Victor OlivasKhaled M Jami 1Anna Moroz 4Benoit Jego 2Emilie Jaumain 2Lawrence FongCharles S CraikAlbert J ChangTrever G BivonaCheng-I Wang 2Michael J Evans 1

Affiliations expand

Free PMC article

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.

Conflict of interest statement

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.

Figures

Figure 1

Figure 1 

Defining the optimal time after…

 Figure 2

Figure 2 

89 Zr-C4 detects PD-L1 expression…

 Figure 3

Figure 3 

89 Zr-C4 can specifically detect…

 Figure 4

Figure 4 

89 Zr-C4 can detect pharmacologically…

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References


    1. 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


    1. 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


    1. 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


    1. 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


    1. 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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • B7-H1 Antigen

  • CD274 protein, human

  • Immunoconjugates

  • Immunoglobulin G

  • Radioisotopes

  • Recombinant Proteins

  • Zirconium

  • Zirconium-89

Related information

Grant support

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Bioconjug Chem

2018 Oct 17;29(10):3476-3482.

 doi: 10.1021/acs.bioconjchem.8b00632. Epub 2018 Sep 24.

A Preclinical Assessment of 89 Zr-atezolizumab Identifies a Requirement for Carrier Added Formulations Not Observed with 89 Zr-C4

Anna Moroz 1 2Chia-Yin Lee 3Yung-Hua Wang 2Jeffrey C Hsiao 2Natalia Sevillano 4Charles Truillet 5Charles S Craik 4Lawrence FongCheng-I Wang 3Michael J Evans 2 4

Affiliations expand

Free PMC article

Abstract

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.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1.

Figure 1.. A summary of the biodistribution…

 Figure 2.

Figure 2.. Added atezo carrier redistributes 89…

 Figure 3.

Figure 3.. Added atezo carrier substantially elevates…

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Cited by

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Publication types

  • Research Support, N.I.H., Extramural

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Antibodies, Monoclonal

  • Antibodies, Monoclonal, Humanized

  • Antineoplastic Agents

  • Drug Carriers

  • Radiopharmaceuticals

  • atezolizumab

  • Zirconium

Related information

Grant support

LinkOut - more resources




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