Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGFβ enhance the efficacy of cancer immunotherapy

Rajani Ravi; Kimberly A. Noonan; Vui Pham; Rishi Bedi; Alex Zhavoronkov; Ivan V. Ozerov; Eugene Makarev; Artem V. Artemov; Piotr T. Wysocki; Ranee Mehra; Sridhar Nimmagadda; Luigi Marchionni; David Sidransky; Ivan M. Borrello; Evgeny Izumchenko; Atul Bedi

doi:10.1038/s41467-017-02696-6

Nature Communications (Feb 2018)

Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGFβ enhance the efficacy of cancer immunotherapy

Rajani Ravi,
Kimberly A. Noonan,
Vui Pham,
Rishi Bedi,
Alex Zhavoronkov,
Ivan V. Ozerov,
Eugene Makarev,
Artem V. Artemov,
Piotr T. Wysocki,
Ranee Mehra,
Sridhar Nimmagadda,
Luigi Marchionni,
David Sidransky,
Ivan M. Borrello,
Evgeny Izumchenko,
Atul Bedi

Affiliations

Rajani Ravi: Department of Otolaryngology–Head and Neck Cancer Research, Johns Hopkins University School of Medicine
Kimberly A. Noonan: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Vui Pham: Department of Otolaryngology–Head and Neck Cancer Research, Johns Hopkins University School of Medicine
Rishi Bedi: Department of Computer Science, Stanford University
Alex Zhavoronkov: Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern
Ivan V. Ozerov: Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern
Eugene Makarev: Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern
Artem V. Artemov: Insilico Medicine, Inc., Emerging Technology Centers, Johns Hopkins University at Eastern
Piotr T. Wysocki: Department of Otolaryngology–Head and Neck Cancer Research, Johns Hopkins University School of Medicine
Ranee Mehra: Department of Oncology, Johns Hopkins University School of Medicine
Sridhar Nimmagadda: Department of Radiology and Radiological Science, Johns Hopkins Medical Institutions
Luigi Marchionni: Center for Computational Genomics, Johns Hopkins University School of Medicine
David Sidransky: Department of Otolaryngology–Head and Neck Cancer Research, Johns Hopkins University School of Medicine
Ivan M. Borrello: Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Evgeny Izumchenko: Department of Otolaryngology–Head and Neck Cancer Research, Johns Hopkins University School of Medicine
Atul Bedi: Department of Otolaryngology–Head and Neck Cancer Research, Johns Hopkins University School of Medicine

DOI: https://doi.org/10.1038/s41467-017-02696-6
Journal volume & issue: Vol. 9, no. 1
pp. 1 – 14

Abstract

Read online

Antitumor T cells can be inhibited by a TGFβ rich tumor microenvironment. The authors develop bifunctional proteins comprising CTLA-4 or PD-L1 immune checkpoint-targeted antibodies fused to a “TGFβ trap” and show that they counteract tumor immune tolerance and enhance the efficacy of these antibodies.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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