A humanized antibody for imaging immune checkpoint ligand PD-L1 expression in tumors

Samit Chatterjee, Wojciech Lesniak, Matthew Gabrielson, Ala Lisok, Bryan Wharram, Polina Sysa-Shah, Babak Behnam Azad, Martin Gilbert Pomper, Sridhar Nimmagadda

Research output: Contribution to journalArticle

Abstract

Antibodies targeting the PD-1/PD-L1 immune checkpoint lead to tumor regression and improved survival in several cancers. PD-L1 expression in tumors may be predictive of response to checkpoint blockade therapy. Because tissue samples might not always be available to guide therapy, we developed and evaluated a humanized antibody for non-invasive imaging of PD-L1 expression in tumors. Radiolabeled [111In]PD-L1-mAb and near-infrared dye conjugated NIR-PD-L1-mAb imaging agents were developed using the mouse and human cross-reactive PD-L1 antibody MPDL3280A. We tested specificity of [111In]PD-L1-mAb and NIR-PD-L1-mAb in cell lines and in tumors with varying levels of PD-L1 expression. We performed SPECT/CT imaging, biodistribution and blocking studies in NSG mice bearing tumors with constitutive PD-L1 expression (CHO-PDL1) and in controls (CHO). Results were confirmed in triple negative breast cancer (TNBC) (MDAMB231 and SUM149) and non-small cell lung cancer (NSCLC) (H2444 and H1155) xenografts with varying levels of PD-L1 expression. There was specific binding of [111In]PD-L1-mAb and NIRPD- L1-mAb to tumor cells in vitro, correlating with PD-L1 expression levels. In mice bearing subcutaneous and orthotopic tumors, there was specific and persistent high accumulation of signal intensity in PD-L1 positive tumors (CHO-PDL1, MDAMB231, H2444) but not in controls. These results demonstrate that [111In]PD-L1-mAb and NIR-PD-L1-mAb can detect graded levels of PD-L1 expression in human tumor xenografts in vivo. As a humanized antibody, these findings suggest clinical translation of radiolabeled versions of MPDL3280A for imaging. Specificity of NIR-PD-L1-mAb indicates the potential for optical imaging of PD-L1 expression in tumors in relevant pre-clinical as well as clinical settings.

Original languageEnglish (US)
Pages (from-to)10215-10227
Number of pages13
JournalOncotarget
Volume7
Issue number9
DOIs
StatePublished - 2016

Fingerprint

Antibodies, Monoclonal, Humanized
Ligands
Neoplasms
Heterografts
Triple Negative Breast Neoplasms
Antibodies
Optical Imaging
Tumor Cell Line
Non-Small Cell Lung Carcinoma
Coloring Agents

Keywords

  • Immune escape
  • Immunotherapy
  • Molecular imaging
  • MPDL3280A
  • Personalized medicine

ASJC Scopus subject areas

  • Oncology

Cite this

A humanized antibody for imaging immune checkpoint ligand PD-L1 expression in tumors. / Chatterjee, Samit; Lesniak, Wojciech; Gabrielson, Matthew; Lisok, Ala; Wharram, Bryan; Sysa-Shah, Polina; Behnam Azad, Babak; Pomper, Martin Gilbert; Nimmagadda, Sridhar.

In: Oncotarget, Vol. 7, No. 9, 2016, p. 10215-10227.

Research output: Contribution to journalArticle

Chatterjee, Samit ; Lesniak, Wojciech ; Gabrielson, Matthew ; Lisok, Ala ; Wharram, Bryan ; Sysa-Shah, Polina ; Behnam Azad, Babak ; Pomper, Martin Gilbert ; Nimmagadda, Sridhar. / A humanized antibody for imaging immune checkpoint ligand PD-L1 expression in tumors. In: Oncotarget. 2016 ; Vol. 7, No. 9. pp. 10215-10227.
@article{389f7489c1334ec88de416e926d56341,
title = "A humanized antibody for imaging immune checkpoint ligand PD-L1 expression in tumors",
abstract = "Antibodies targeting the PD-1/PD-L1 immune checkpoint lead to tumor regression and improved survival in several cancers. PD-L1 expression in tumors may be predictive of response to checkpoint blockade therapy. Because tissue samples might not always be available to guide therapy, we developed and evaluated a humanized antibody for non-invasive imaging of PD-L1 expression in tumors. Radiolabeled [111In]PD-L1-mAb and near-infrared dye conjugated NIR-PD-L1-mAb imaging agents were developed using the mouse and human cross-reactive PD-L1 antibody MPDL3280A. We tested specificity of [111In]PD-L1-mAb and NIR-PD-L1-mAb in cell lines and in tumors with varying levels of PD-L1 expression. We performed SPECT/CT imaging, biodistribution and blocking studies in NSG mice bearing tumors with constitutive PD-L1 expression (CHO-PDL1) and in controls (CHO). Results were confirmed in triple negative breast cancer (TNBC) (MDAMB231 and SUM149) and non-small cell lung cancer (NSCLC) (H2444 and H1155) xenografts with varying levels of PD-L1 expression. There was specific binding of [111In]PD-L1-mAb and NIRPD- L1-mAb to tumor cells in vitro, correlating with PD-L1 expression levels. In mice bearing subcutaneous and orthotopic tumors, there was specific and persistent high accumulation of signal intensity in PD-L1 positive tumors (CHO-PDL1, MDAMB231, H2444) but not in controls. These results demonstrate that [111In]PD-L1-mAb and NIR-PD-L1-mAb can detect graded levels of PD-L1 expression in human tumor xenografts in vivo. As a humanized antibody, these findings suggest clinical translation of radiolabeled versions of MPDL3280A for imaging. Specificity of NIR-PD-L1-mAb indicates the potential for optical imaging of PD-L1 expression in tumors in relevant pre-clinical as well as clinical settings.",
keywords = "Immune escape, Immunotherapy, Molecular imaging, MPDL3280A, Personalized medicine",
author = "Samit Chatterjee and Wojciech Lesniak and Matthew Gabrielson and Ala Lisok and Bryan Wharram and Polina Sysa-Shah and {Behnam Azad}, Babak and Pomper, {Martin Gilbert} and Sridhar Nimmagadda",
year = "2016",
doi = "10.18632/oncotarget.7143",
language = "English (US)",
volume = "7",
pages = "10215--10227",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "9",

}

TY - JOUR

T1 - A humanized antibody for imaging immune checkpoint ligand PD-L1 expression in tumors

AU - Chatterjee, Samit

AU - Lesniak, Wojciech

AU - Gabrielson, Matthew

AU - Lisok, Ala

AU - Wharram, Bryan

AU - Sysa-Shah, Polina

AU - Behnam Azad, Babak

AU - Pomper, Martin Gilbert

AU - Nimmagadda, Sridhar

PY - 2016

Y1 - 2016

N2 - Antibodies targeting the PD-1/PD-L1 immune checkpoint lead to tumor regression and improved survival in several cancers. PD-L1 expression in tumors may be predictive of response to checkpoint blockade therapy. Because tissue samples might not always be available to guide therapy, we developed and evaluated a humanized antibody for non-invasive imaging of PD-L1 expression in tumors. Radiolabeled [111In]PD-L1-mAb and near-infrared dye conjugated NIR-PD-L1-mAb imaging agents were developed using the mouse and human cross-reactive PD-L1 antibody MPDL3280A. We tested specificity of [111In]PD-L1-mAb and NIR-PD-L1-mAb in cell lines and in tumors with varying levels of PD-L1 expression. We performed SPECT/CT imaging, biodistribution and blocking studies in NSG mice bearing tumors with constitutive PD-L1 expression (CHO-PDL1) and in controls (CHO). Results were confirmed in triple negative breast cancer (TNBC) (MDAMB231 and SUM149) and non-small cell lung cancer (NSCLC) (H2444 and H1155) xenografts with varying levels of PD-L1 expression. There was specific binding of [111In]PD-L1-mAb and NIRPD- L1-mAb to tumor cells in vitro, correlating with PD-L1 expression levels. In mice bearing subcutaneous and orthotopic tumors, there was specific and persistent high accumulation of signal intensity in PD-L1 positive tumors (CHO-PDL1, MDAMB231, H2444) but not in controls. These results demonstrate that [111In]PD-L1-mAb and NIR-PD-L1-mAb can detect graded levels of PD-L1 expression in human tumor xenografts in vivo. As a humanized antibody, these findings suggest clinical translation of radiolabeled versions of MPDL3280A for imaging. Specificity of NIR-PD-L1-mAb indicates the potential for optical imaging of PD-L1 expression in tumors in relevant pre-clinical as well as clinical settings.

AB - Antibodies targeting the PD-1/PD-L1 immune checkpoint lead to tumor regression and improved survival in several cancers. PD-L1 expression in tumors may be predictive of response to checkpoint blockade therapy. Because tissue samples might not always be available to guide therapy, we developed and evaluated a humanized antibody for non-invasive imaging of PD-L1 expression in tumors. Radiolabeled [111In]PD-L1-mAb and near-infrared dye conjugated NIR-PD-L1-mAb imaging agents were developed using the mouse and human cross-reactive PD-L1 antibody MPDL3280A. We tested specificity of [111In]PD-L1-mAb and NIR-PD-L1-mAb in cell lines and in tumors with varying levels of PD-L1 expression. We performed SPECT/CT imaging, biodistribution and blocking studies in NSG mice bearing tumors with constitutive PD-L1 expression (CHO-PDL1) and in controls (CHO). Results were confirmed in triple negative breast cancer (TNBC) (MDAMB231 and SUM149) and non-small cell lung cancer (NSCLC) (H2444 and H1155) xenografts with varying levels of PD-L1 expression. There was specific binding of [111In]PD-L1-mAb and NIRPD- L1-mAb to tumor cells in vitro, correlating with PD-L1 expression levels. In mice bearing subcutaneous and orthotopic tumors, there was specific and persistent high accumulation of signal intensity in PD-L1 positive tumors (CHO-PDL1, MDAMB231, H2444) but not in controls. These results demonstrate that [111In]PD-L1-mAb and NIR-PD-L1-mAb can detect graded levels of PD-L1 expression in human tumor xenografts in vivo. As a humanized antibody, these findings suggest clinical translation of radiolabeled versions of MPDL3280A for imaging. Specificity of NIR-PD-L1-mAb indicates the potential for optical imaging of PD-L1 expression in tumors in relevant pre-clinical as well as clinical settings.

KW - Immune escape

KW - Immunotherapy

KW - Molecular imaging

KW - MPDL3280A

KW - Personalized medicine

UR - http://www.scopus.com/inward/record.url?scp=84961666341&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84961666341&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.7143

DO - 10.18632/oncotarget.7143

M3 - Article

C2 - 26848870

AN - SCOPUS:84961666341

VL - 7

SP - 10215

EP - 10227

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 9

ER -