Goldilocks and the Three Trials: Clinical Trials Targeting the αβ Integrin in Idiopathic Pulmonary Fibrosis

Overview

Journal Am J Respir Crit Care Med

Specialty Critical Care

Date 2022 Aug 26

PMID 36018580

Authors

Patricia Sime

Gisli Jenkins

Affiliations

Soon will be listed here.

Citing Articles

Pulmonary fibroelastosis - A review.

Yombo D, Madala S, Vemulapalli C, Ediga H, Hardie W Matrix Biol. 2023; 124:1-7.

PMID: 37922998 PMC: 10841596. DOI: 10.1016/j.matbio.2023.10.003.

De novo design of highly selective miniprotein inhibitors of integrins αvβ6 and αvβ8.

Roy A, Shi L, Chang A, Dong X, Fernandez A, Kraft J Nat Commun. 2023; 14(1):5660.

PMID: 37704610 PMC: 10500007. DOI: 10.1038/s41467-023-41272-z.

Cell Adhesion Molecules in Fibrotic Diseases.

Hu Q, Saleem K, Pandey J, Charania A, Zhou Y, He C Biomedicines. 2023; 11(7).

PMID: 37509634 PMC: 10377070. DOI: 10.3390/biomedicines11071995.

design of highly selective miniprotein inhibitors of integrins αvβ6 and αvβ8.

Roy A, Shi L, Chang A, Dong X, Fernandez A, Kraft J bioRxiv. 2023; .

PMID: 37398153 PMC: 10312613. DOI: 10.1101/2023.06.12.544624.

References

Mitra M, Lancaster K, Adedeji A, Palanisamy G, Dave R, Zhong F . A Potent Pan-TGFβ Neutralizing Monoclonal Antibody Elicits Cardiovascular Toxicity in Mice and Cynomolgus Monkeys. Toxicol Sci. 2020; 175(1):24-34. DOI: 10.1093/toxsci/kfaa024. View

Raghu G, Mouded M, Prasse A, Stebbins C, Zhao G, Song G . Randomized Phase IIa Clinical Study of an Anti-αβ Monoclonal Antibody in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2022; 206(9):1166-1168. PMC: 9704833. DOI: 10.1164/rccm.202205-0868LE. View

Koivisto L, Bi J, Hakkinen L, Larjava H . Integrin αvβ6: Structure, function and role in health and disease. Int J Biochem Cell Biol. 2018; 99:186-196. DOI: 10.1016/j.biocel.2018.04.013. View

Reed N, Jo H, Chen C, Tsujino K, Arnold T, DeGrado W . The αvβ1 integrin plays a critical in vivo role in tissue fibrosis. Sci Transl Med. 2015; 7(288):288ra79. PMC: 4461057. DOI: 10.1126/scitranslmed.aaa5094. View

Munger J, Huang X, Kawakatsu H, Griffiths M, Dalton S, Wu J . The integrin alpha v beta 6 binds and activates latent TGF beta 1: a mechanism for regulating pulmonary inflammation and fibrosis. Cell. 1999; 96(3):319-28. DOI: 10.1016/s0092-8674(00)80545-0. View

Horan G, Wood S, Ona V, Li D, Lukashev M, Weinreb P . Partial inhibition of integrin alpha(v)beta6 prevents pulmonary fibrosis without exacerbating inflammation. Am J Respir Crit Care Med. 2007; 177(1):56-65. DOI: 10.1164/rccm.200706-805OC. View

Raghu G, Mouded M, Chambers D, Martinez F, Richeldi L, Lancaster L . A Phase IIb Randomized Clinical Study of an Anti-αβ Monoclonal Antibody in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2022; 206(9):1128-1139. DOI: 10.1164/rccm.202112-2824OC. View

Saini G, Porte J, Weinreb P, Violette S, Wallace W, McKeever T . αvβ6 integrin may be a potential prognostic biomarker in interstitial lung disease. Eur Respir J. 2015; 46(2):486-94. DOI: 10.1183/09031936.00210414. View

Koth L, Alex B, Hawgood S, Nead M, Sheppard D, Erle D . Integrin beta6 mediates phospholipid and collectin homeostasis by activation of latent TGF-beta1. Am J Respir Cell Mol Biol. 2007; 37(6):651-9. PMC: 2219547. DOI: 10.1165/rcmb.2006-0428OC. View

10.

Morris D, Huang X, Kaminski N, Wang Y, Shapiro S, Dolganov G . Loss of integrin alpha(v)beta6-mediated TGF-beta activation causes Mmp12-dependent emphysema. Nature. 2003; 422(6928):169-73. DOI: 10.1038/nature01413. View

11.

John A, Graves R, Pun K, Vitulli G, Forty E, Mercer P . Translational pharmacology of an inhaled small molecule αvβ6 integrin inhibitor for idiopathic pulmonary fibrosis. Nat Commun. 2020; 11(1):4659. PMC: 7494911. DOI: 10.1038/s41467-020-18397-6. View