Fast Image-Guided Stratification Using Anti-Programmed Death Ligand 1 Gold Nanoparticles for Cancer Immunotherapy

Rinat Meir, Katerina Shamalov, Tamar Sadan, Menachem Motiei, Gur Yaari, Cyrille J. Cohen, Rachela Popovtzer

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

Cancer immunotherapy has made enormous progress in offering safer and more effective treatments for the disease. Specifically, programmed death ligand 1 antibody (αPDL1), designed to perform immune checkpoint blockade (ICB), is now considered a pillar in cancer immunotherapy. However, due to the complexity and heterogeneity of tumors, as well as the diversity in patient response, ICB therapy only has a 30% success rate, at most; moreover, the efficacy of ICB can be evaluated only two months after start of treatment. Therefore, early identification of potential responders and nonresponders to therapy, using noninvasive means, is crucial for improving treatment decisions. Here, we report a straightforward approach for fast, image-guided prediction of therapeutic response to ICB. In a colon cancer mouse model, we demonstrate that the combination of computed tomography imaging and gold nanoparticles conjugated to αPDL1 allowed prediction of therapeutic response, as early as 48 h after treatment. This was achieved by noninvasive measurement of nanoparticle accumulation levels within the tumors. Moreover, we show that the nanoparticles efficiently prevented tumor growth with only a fifth of the standard dosage of clinical care. This technology may be developed into a powerful tool for early and noninvasive patient stratification as responders or nonresponders.

Original languageEnglish
Pages (from-to)11127-11134
Number of pages8
JournalACS Nano
Volume11
Issue number11
DOIs
StatePublished - 28 Nov 2017

Bibliographical note

Publisher Copyright:
© 2017 American Chemical Society.

Funding

We thank the Ministry of Science, Technology and Space for R.M.’s doctoral scholarship. We thank Merkel Technologies for conducting the Particle Matrix experiments and Michal Marcus for conducting the Bradford assay.

FundersFunder number
Ministry of Science, Technology and Space

    Keywords

    • cancer immunotherapy
    • computed tomography
    • gold nanoparticles
    • imaging
    • stratification
    • αPDL1

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