This study is a single-arm, open-label, dose-escalation clinical trial to evaluate the safety, tolerability, changes and persistence of peripheral blood Treg cells, and pharmacodynamic characteristics of donor-derived Treg cell injection combined with recombinant human interleukin-2 in treating subjects with refractory cGVHD，and to preliminarily observe the efficacy of the study drugs in subjects with refractory cGVHD.
Subjects aged 18-70 years old, male or female;
The subjects had received allo-HSCT, including cord blood transplantation;
There was no improvement in cGVHD in initial treatment patients treated with > 0.5mg/kg/ day or 1 mg/kg/ day every other day for at least 4 weeks;
Steroid dependence: predtisone dose > 0.25 mg/kg/d or > 0.5 mg/kg/qod cGVHD relapse or progression; cGVHD recurred after two attempts to gradually reduce prednisone dose at an interval of at least 8 weeks, with prednisone dose > 0.25 mg/kg/day to be maintained.
Subjects had a recurrence of primary malignant disease before receiving Treg treatment;
The subjects had persistent, recurrent or delayed aGVHD;
Continuous use of prednisone >1 mg/kg/day is required;
The severity of the subject's cGVHD cannot be assessed by physical examination or laboratory examination;
Single group
Donor-derived Treg cell injection combined with interleukin 2
Biological/VaccineSubjects received Treg cell infusion at day D0, and interleukin 2 was administered subcutaneously daily from 1 week before to 12 weeks after infusion.
To evaluate the incidence of DLT in patients with refractory cGVHD treated with donor-derived Treg cell injection combined with low dose rhIL-2 injection
To evaluate the incidence of DLT in patients with refractory cGVHD treated with donor-derived Treg cell injection combined with low dose rhIL-2 injection。 DLT is defined as any of the following conditions related to the study drug within 28 days after the subject's infusion of Treg cell injection, despite treatment: 1. Grade 4 or 5 cytokine release syndrome caused by Treg cell injection treatment; 2. Grade 3 cytokine syndrome caused by Treg cell injection treatment and no remission to grade 2 or below within 7 days; 3. Occurrence of grade 3 or higher neurotoxicity; 4. Grade 4 hematologic toxicity: caused by non-underlying disease and lasting ≥ 28 days (except for lymphopenia, neutrophil and thrombocytopenia caused by chemotherapy pretreatment); 5. Any unanticipated toxicity that necessitates discontinuation of treatment at the discretion of the investigator or collaborating unit.
Incidence of grade 3 and above adverse reactions
Incidence of adverse events associated with the study products；Adverse events assessed according to NCI-CTCAE v5.0.
Evaluate the number of Treg cells in subjects' peripheral blood
Evaluate the number of Treg cells in subjects' peripheral blood after donor-derived Treg cell injection administration
Analysis of the number changes of lymphocyte subsets in peripheral blood.
Analysis of the number changes of lymphocyte subsets in peripheral blood, Including T/B/NK cells.
Score changes in the 36-Item Short Form Health Survey (SF-36)
Adopt 36-Item Short Form Survey (SF-36)to analyze the changes in patients' scores after medication compared with baseline.
Score changes in Lee Chronic Graft-versus-Host Disease Symptom Scale
Adopt 36-Item Short Form Survey (SF-36)to analyze the changes in patients' scores after medication compared with baseline.
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