| Title: |
P999 First in human treatment of Crohn’s disease with autologous ex-vivo expanded polyclonal, gut-targeted regulatory T cells: Initial results of the TRIBUTE feasibility study |
| Authors: |
Irving, P M; Seah, D; Centritto, A; Clough, J; Canavan, J; Goldberg, R; Prevost, A T; Vasconcelos, J C; Lyne, M; Palmer Joyce, J; Patel, P; Tasker, S; Marks, P; Rodger, B; Jackson, I; Macallan, D; Ong, M; Sutcliffe, M; Travis, M; Lord, G |
| Source: |
Journal of Crohn's and Colitis ; volume 18, issue Supplement_1, page i1803-i1803 ; ISSN 1873-9946 1876-4479 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2024 |
| Description: |
Background Despite the increase in novel medications for Crohn’s disease (CD), many patients either fail to respond adequately to, or are intolerant of current drugs. Cell therapies have yet to have a significant impact in IBD but represent a potential novel treatment option. Regulatory T-cells (Tregs) play a key role in immune homeostasis, and Treg dysfunction is implicated in the pathogenesis of CD. Their therapeutic potential has not been assessed in humans with CD. We designed a Phase 1b study to explore the feasibility of using novel, autologous, ex-vivo expanded, gut-homing Tregs as a treatment for CD. Methods The TRIBUTE feasibility study aimed to treat 4 patients with treatment-refractory, moderate to severe CD (CDAI 220-450 and endoscopic ulceration) with a single dose of 3-5x106 cells/kg of TR004, an autologous cell product comprising CD4+CD25+CD127lowCD45RA+ Tregs expanded ex-vivo in the presence of an agonist that increases the expression of a4b7, priming the cells for gut homing. Deuteration during expansion allowed for cell tracking. Primary outcomes were dose-limiting toxicity by week 5, feasibility of recruitment to and retention in the study, successful expansion of the cells and successful dosing. Colonoscopy was performed at screening and at week (wk) 8 and disease activity (CDAI and biomarkers) was assessed at wk 0,1,2,3,5 and 8. Safety follow up is planned to wk 104. Results 5 patients (3 male, median age 36 (range 24-39), median failed advanced therapies 3 (2-4)) were screened. In 1 patient, cells failed at day 21 of expansion due to human error requiring the patient to be replaced. Of the 4 patients with successful expansion of cells, after 23-30 days of expansion, median b7 expression was 98% (92-99%) and cell viability was 91% (84-94%). Median fold expansion was 254 (32-578). 3 patients received a dose of TR004 and attended all study visits, the other patient being withdrawn prior to dosing due to pregnancy after contraceptive failure. No dose-limiting toxicities occurred. 1 ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/ecco-jcc/jjad212.1129 |
| Availability: |
https://doi.org/10.1093/ecco-jcc/jjad212.1129; https://academic.oup.com/ecco-jcc/article-pdf/18/Supplement_1/i1803/56349534/jjad212.1129.pdf |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.32A69BD6 |
| Database: |
BASE |