Treatment of advanced gastrointestinal cancer with genetically modified autologous mesenchymal stem cells: Results from the phase 1/2 TREAT‐ME‐1 trial

Abstract

TREAT‐ME‐1, a Phase 1/2 open‐label multicenter, first‐in‐human, first‐in‐class trial, evaluated the safety, tolerability and efficacy of treatment with genetically modified autologous mesenchymal stromal cells (MSC), MSC_ apceth_101, in combination with ganciclovir in patients with advanced gastrointestinal adenocarcinoma. Immunological and inflammatory markers were also assessed. All patients (3 in Phase 1; 7 in Phase 2) received three treatment cycles of MSC_apceth_101 at one dose level on Day 0, 7, and 14 followed by ganciclovir administration according to the manufacturer's instructions for 48─72 h after MSC_apceth_101 injection. Ten patients were treated with a total dose of 3.0 x 106 cells/kg MSC_apceth_101. 36 adverse events and six serious adverse events were reported. Five patients achieved stable disease (change in target lesions of −2 to +28%). For all patients, the median time to progression was 1.8 months (95% CI: 0.5, 3.9 months). Median overall survival could not be estimated as 8/10 patients were still alive at the end of the study (1 year) and therefore censored. Post‐study observation of patients showed a median overall survival of 15.6 months (ranging from 2.2─27.0 months). Treatment with MSC_apceth_101 and ganciclovir did not induce a consistent increase or decrease in levels of any of the tumor markers analyzed. No clear trends in the immunological markers assessed were observed. MSC_apceth_101 in combination with ganciclovir was safe and tolerable in patients with advanced gastrointestinal adenocarcinoma, with preliminary signs of efficacy in terms of clinical stabilization of disease.

The morphology and application of stem cells in digestive system surgery

“…The therapy was confirmed to be acceptably safe and tolerable, which was consistent with Phase 1 study results [47]. Study presented signs of activity with stable disease in five of ten patients, however no impact on tumor markers and size was observed [48].…”

A facile and scalable in production non-viral gene engineered mesenchymal stem cells for effective suppression of temozolomide-resistant (TMZR) glioblastoma growth

“…Depending on the route of administration, it may require up to 4 days for MSCs to nest around the tumour foci [33]. In a recent report, prodrug was administered 48-72 h after modified MSC administration to allow sufficient time for nesting of MSCs into the tumour vicinity [45]. We next examined the duration of the transgene expression.…”

“…In the present study, we developed a facile, rapid and scalable transfection protocol to generate MSCs producing CD::UPRT::GFP. Without the need for antibiotic selection, the quality of the engineered cells satisfied the release criteria reported in recent CDEPT clinical trials [18,45]. To be more clinically relevant, this study examined the cytotoxic effects of this non-viral engineered MSCs on TMZ-sensitive and TMZ-resistant GBM as well as the uniquely characterized and clinically annotated GBM cell lines derived from patient surgical samples.…”

Genetic Engineering as a Strategy to Improve the Therapeutic Efficacy of Mesenchymal Stem/Stromal Cells in Regenerative Medicine

“…Also an enhancement in TNFα/IL-10 ratio, which suggests a higher inflammatory effectiveness and an anti-tumor capacity, was observed in 5 patients as well (von Einem et al, 2019).…”