Production, safety and efficacy of iPSC-derived mesenchymal stromal cells in acute steroid-resistant graft versus host disease: a phase I, multicenter, open-label, dose-escalation study

Production, safety and efficacy of iPSC-derived mesenchymal stromal cells in acute steroid-resistant graft versus host disease: a phase I, multicenter, open-label, dose-escalation study.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.1038/s41591-020-1050-x
Journal or Publication Title: Nature Medicine
Volume: 26
Number: 11
Page Range: pp. 1720-1725
Date: 2020
Divisions: Gene and Stem Cell Therapy
Depositing User: General Admin
Identification Number: 10.1038/s41591-020-1050-x
ISSN: 1078-8956
Date Deposited: 04 Jan 2021 03:05
Abstract:

The therapeutic potential of donor-derived mesenchymal stromal cells (MSCs) has been investigated in diverse diseases1, including steroid-resistant acute graft versus host disease (SR-aGvHD)2. However, conventional manufacturing approaches are hampered by challenges with scalability and interdonor variability, and clinical trials have shown inconsistent outcomes3,4. Induced pluripotent stem cells (iPSCs) have the potential to overcome these challenges, due to their capacity for multilineage differentiation and indefinite proliferation5,6. Nonetheless, human clinical trials of iPSC-derived cells have not previously been completed. CYP-001 (iPSC-derived MSCs) is produced using an optimized, good manufacturing practice (GMP)-compliant manufacturing process. We conducted a phase 1, open-label clinical trial (no. NCT02923375) in subjects with SR-aGvHD. Sixteen subjects were screened and sequentially assigned to cohort A or cohort B (n = 8 per group). One subject in cohort B withdrew before receiving CYP-001 and was excluded from analysis. All other subjects received intravenous infusions of CYP-001 on days 0 and 7, at a dose level of either 1 × 106 cells per kg body weight, to a maximum of 1 × 108 cells per infusion (cohort A), or 2 × 106 cells per kg body weight, to a maximum dose of 2 × 108 cells per infusion (cohort B). The primary objective was to assess the safety and tolerability of CYP-001, while the secondary objectives were to evaluate efficacy based on the proportion of participants who showed a complete response (CR), overall response (OR) and overall survival (OS) by days 28/100. CYP-001 was safe and well tolerated. No serious adverse events were assessed as related to CYP-001. OR, CR and OS rates by day 100 were 86.7, 53.3 and 86.7%, respectively. The therapeutic application of iPSC-derived MSCs may now be explored in diverse inflammatory and immune-mediated diseases.

Creators:
Creators
Email
Bloor, Adrian J. C.
UNSPECIFIED
Patel, Amit
UNSPECIFIED
Griffin, James E.
UNSPECIFIED
Gilleece, Maria H.
UNSPECIFIED
Radia, Rohini
UNSPECIFIED
Yeung, David T.
UNSPECIFIED
Drier, Diana
UNSPECIFIED
Larson, Laurie S.
UNSPECIFIED
Uenishi, Gene I.
UNSPECIFIED
Hei, Derek
UNSPECIFIED
Kelly, Kilian
UNSPECIFIED
Slukvin, Igor
UNSPECIFIED
Rasko, John E. J.
UNSPECIFIED
Last Modified: 04 Jan 2021 03:05
URI: https://eprints.centenary.org.au/id/eprint/757

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