This study is a single-arm, single-center, open-label, dose-escalation exploratory clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of CD19 CAR-γδ T cells. The subjects enrolled in this study are patients with relapsed/refractory autoimmune nephropathy, including lupus nephritis, IgA nephropathy, and membranous nephropathy. This study adopts a standard "3+3" design to assess the recommended dose (RD) and identify dose-limiting toxicities (DLTs). The treatment process is as follows: subjects who meet the inclusion criteria will receive lymphodepletion conditioning, followed by a single intravenous infusion of CD19 CAR-γδ T cells. The primary objective of this study is to evaluate the safety profile of this cellular therapy, including the incidence of DLTs, maximum tolerated dose (MTD) or RD, as well as the incidence and severity of treatment-related adverse events and clinically significant abnormal laboratory test results after CAR-γδ T cell infusion (including the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS)). The planned follow-up duration of this study is 1 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Prior to CAR-γδ T cell infusion, patients will receive lymphodepleting chemotherapy consisting of cyclophosphamide combined with fludarabine, followed by infusion of CD19 CAR-γδ T cells at the assigned dose level per their dose-escalation cohort, with target total cell doses of 3×10\^7, 1×10\^8, and 3×10\^8 cells, respectively.
Xijing Hospital
Xi'an, Shaanxi, China
Incidence of Dose-Limiting Toxicities (DLTs)
The number, frequency, and severity of DLTs experienced by subjects after the first infusion of CD19 CAR-γδ T cells. DLTs are defined by NCI-CTCAE 5.0 and ASTCT consensus for CRS and neurotoxicity.
Time frame: Day 0 to Day 28 post-infusion
Incidence of Adverse Events (AEs)
Evaluation of the number, frequency, and severity of all adverse events, including Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events (TRAEs), and Serious Adverse Events (SAEs).
Time frame: Up to Month 12 post-infusion
Preliminary Clinical Efficacy for Lupus Nephritis
Proportion of subjects achieving complete renal response, major renal response, and partial renal response.
Time frame: Month 3, Month 6, Month 9, Month 12,
Preliminary Clinical Efficacy for IgA Nephropathy
Proportion of subjects with 24-hour urine protein quantification below the threshold of 0.3g/24h.
Time frame: Month 3, Month 6, Month 9, Month 12,
Preliminary Clinical Efficacy for Membranous Nephropathy
Proportion of subjects achieving complete remission (CR) or partial remission (PR).
Time frame: Month 3, Month 6, Month 9, Month 12
The degree of B cell depletion
The degree of B cell depletion at various time points
Time frame: Up to 12 Months After CAR-γδT Cell Infusion
Urine Protein
Change from baseline in 24-hour urine protein quantification following a single infusion of CD19 CAR-γδ T Cell
Time frame: Week 2, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 12
Antoantibody
Changes and seronegative rates of serum autoantibodies (e.g., anti-dsDNA antibody, anti-Sm antibody, anti-PLA2R antibody, etc.) from baseline following infusion
Time frame: Week 2, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 12
Serum Albumin
Changes in serum albumin levels from baseline following infusion
Time frame: Week 2, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 12
eGFR
Change from baseline in estimated glomerular filtration rate(eGFR) quantification following a single infusion of CD19 CAR-T cells
Time frame: Week 2, Month 1, Month 2, Month 3, Month 4, Month 5, Month 6, Month 12
Cmax of CAR-T cells
The peak plasma concentration (Cmax) of amplified CAR-γδ T cells in peripheral blood after infusion.
Time frame: Within 28 Days After CAR-γδ T Cell Infusion
Tmax of CAR-T cells
The time of amplified CAR-γδ T cells in peripheral blood to reach the maximum concentration (Tmax).
Time frame: Within 28 Days After CAR-γδ T Cell Infusion
AUC 0-28d of CAR-T cells
The area under the plasma concentration-time curve from 0 to 28 days after infusion (AUC0-28d).
Time frame: Within 28 Days After CAR-γδ T Cell Infusion
The concentration levels of IL-6
CAR-γδ T-related serum cytokines include IL-6.
Time frame: Up to 6 Months After UCAR T-cell Infusion, and at Month 12
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.