CX601, Allogeneic Expanded Adipose-Derived Mesenchymal Stem Cells (EASC), for Complex Perianal Fistulas in Crohn's Disease: Long-Term Results from a Phase III Randomized Controlled Trial

Panés, Julián; Garcı́a-Olmo, Damián; Assche, Gert A. Van; Colombel, Jean Fréd́eric; Reinisch, Walter; Baumgart, Daniel C.; Nachury, Maria; Ferrante, Marc; Kazemi-Shirazi, Lili; Grimaud, Jean–Charles; Portilla, Fernando de la; Goldin, Eran; Richard, M; Tagarro, Ignacio; Danese, Silvio

doi:10.1016/s0016-5085(17)30934-4

Cited by 13 publications

(34 citation statements)

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“…week 52 [13,14]. This new local option will probably represent the reference therapy in the near future.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, a randomized, double blind controlled trial has shown that a single intralesional injection of allogeneic, expanded, adipose‐derived stem cells shows a significant increase in combined remission rate (clinical and MRI) of 51.5% at week 24 and 56.3 at week 52 [13,14]. This new local option will probably represent the reference therapy in the near future.…”

Section: Discussionmentioning

confidence: 99%

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Long‐term efficacy of fibrin glue injection for perianal fistulas in patients with Crohn's disease

et al. 2020

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Nearly half of Crohn's disease (CD) patients will develop anal lesions [1]. Despite extensive use of immunosuppressants, the treatment of perianal fistulizing CD remains challenging. Decision making mainly depends on the type of fistula (simple or complex), the coexistence of anal abscess and the location and activity of the luminal disease [2]. Combined therapy associating first-line setons followed by antitumour necrosis factor (anti-TNF) represents the standard of care [3]. However, the complete fistula closure rate after infliximab induction is 55% [4] and the rate of closure at 1 year of maintenance treatment is 36% [5]. Various local approaches have been proposed

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“…week 52 [13,14]. This new local option will probably represent the reference therapy in the near future.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Long‐term efficacy of fibrin glue injection for perianal fistulas in patients with Crohn's disease

et al. 2020

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“…MSCs exhibit low immunogenicity, displaying low levels of major histocompatibility complex (MHC) I and an absence of MHC II and costimulatory molecules (17,18), and were therefore considered adequate candidates for allogeneic cell therapy, alleviating the need for the generation of autologous MSC. Locally injected allogeneic MSCs have shown to be useful for the treatment of refractory perianal fistulas in CD (12,13,19) and Alofisel® (Cx601 / darvadstrocel) has now been approved by the European Medicine Agency for the treatment of CD-associated perianal fistulas (12,20). Moreover, previously, we showed the capability of endoscopically injected MSCs to alleviate experimental colitis in mice (21).…”

Section: Mesenchymal Stromal Cells (Mscs) Have Already Shown Great Pr...mentioning

confidence: 93%

Local administration of mesenchymal stromal cells is safe and modulates the immune compartment in ulcerative proctitis

Ouboter¹,

Barnhoorn²,

Verspaget³

et al. 2023

JCI Insight

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BackgroundDue to their immunoregulatory and tissue regenerative features, mesenchymal stromal cells (MSCs) are a promising novel tool for the management of ulcerative proctitis (UP). Here we report on a phase IIa clinical study to evaluate the impact of local MSC therapy in UP. MethodsThirteen refractory UP patients, with endoscopic Mayo score (EMS) 2 or 3, were included. Seven patients received 20-40 x 10 6 allogeneic MSCs (cohort 1), while six patients received 40-80 x 10 6 MSCs (cohort 2). Adverse events (AEs) were assessed at baseline and week 2, 6, 12, and 24. Clinical, endoscopic, and biochemical parameters were assessed at baseline, week 2 and 6. Furthermore, we evaluated the engraftment of MSCs, presence of donor-specific human leukocyte antigen (HLA) antibodies (DSAs), and we determined the impact of MSC therapy on the local immune compartment. ResultsNo serious AEs were observed. The clinical Mayo score was significantly improved at week 2 and 6, and the EMS was significantly improved at week 6, compared to baseline. At week 6, donor MSCs were still detectable in rectum biopsies of 4/9 patients and DSAs against both HLA-class I and -class II were found. Mass cytometry showed a reduction of activated CD8 + T cells and CD16 + monocytes and an enrichment in mononuclear phagocytes and natural killer cells in biopsies after local MSC therapy. ConclusionLocal administration of allogeneic MSCs is safe, tolerable, and feasible for treatment of refractory UP and shows encouraging signs of clinical efficacy and modulation of local immune responses. This sets the stage for larger clinical trials.

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“…Moreover, an official approval for Darvadstrocel (Alofisel), an adipose human MSC injection, was granted by the European commission for the management of complex perianal fistulas in adult patients with mildly or non-active luminal Crohn's disease (European Medicines Agency, 2018b; Panés et al, 2018). The approval emanated from a Phase III trial reporting that Darvadstrocel led to 50% combined remission, which was maintained after 1 year of treatment, in comparison with 34% in the control arm (Panés et al, 2016(Panés et al, , 2018Panes et al, 2017). Interestingly, several "orphan designation" approvals were granted by the European commission according to certain guidelines for the use of human MSCs in the treatment of GvHD, thromboangiitis obliterans (Buerger disease), and ALS (Yu et al, 2018 According to their study, the effectiveness of MSC-FFM is due to donor selection in addition to strict collection and preparation processes (Bader et al, 2018), which yield adequate doses of MSCs with high batch-to-batch consistency (Elgaz et al, 2019).…”

Section: Immune-based Disordersmentioning

confidence: 99%

Mesenchymal Stem Cells Beyond Regenerative Medicine

Shammaa

El-Kadiry

Abusarah

et al. 2020

Front. Cell Dev. Biol.

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Mesenchymal stem cells (MSCs) are competent suitors of cellular therapy due to their therapeutic impact on tissue degeneration and immune-based pathologies. Additionally, their homing and immunomodulatory properties can be exploited in cancer malignancies to transport pharmacological entities, produce anti-neoplastic agents, or induce antitumor immunity. Herein, we create a portfolio for MSC properties, showcasing their distinct multiple therapeutic utilities and successes/challenges thereof in both animal studies and clinical trials. We further highlight the promising potential of MSCs not only in cancer management but also in instigating tumor-specific immunityi.e., cancer vaccination. Finally, we reflect on the possible reasons impeding the clinical advancement of MSC-based cancer vaccines to assist in contriving novel methodologies from which a therapeutic milestone might emanate.

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CX601, Allogeneic Expanded Adipose-Derived Mesenchymal Stem Cells (EASC), for Complex Perianal Fistulas in Crohn's Disease: Long-Term Results from a Phase III Randomized Controlled Trial

Cited by 13 publications

References 0 publications

Long‐term efficacy of fibrin glue injection for perianal fistulas in patients with Crohn's disease

Long‐term efficacy of fibrin glue injection for perianal fistulas in patients with Crohn's disease

Local administration of mesenchymal stromal cells is safe and modulates the immune compartment in ulcerative proctitis

Mesenchymal Stem Cells Beyond Regenerative Medicine

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