Allogeneic CD19/BCMA CAR-T for B Cell-Related Autoimmune Disease

* 1\. Background and Rationale * This study investigates a novel cell therapy for patients with relapsed or refractory B-cell-mediated autoimmune diseases (AID). QT-219C Cell Injection is a universal allogeneic CAR-T cell product derived from healthy donors, designed to target both CD19 and BCMA. * Dual-Targeting Design: By targeting both CD19+ B cells and BCMA+ plasma cells, the therapy aims to achieve deep and extensive depletion of pathogenic immune cells, potentially leading to immune "resetting". * Advanced Gene Editing: * Safety: The TRAC gene is knocked out to eliminate T-cell receptor (TCR) expression, thereby minimizing the risk of Graft-versus-Host Disease (GvHD). Immune Evasion: Genes including CIITA, HLA-A, HLA-B, and HLA-C are knocked out, while HLA-E is retained and a novel hypo-Y element is knocked in to reduce immunogenicity and resist rejection by host T and NK cells. * Enhanced Potency: The gene-X element is integrated to improve the expansion and persistence of the cells within the patient's body, even under conditions of reduced or no lymphodepletion. * 2\. Study Objectives * Primary Objective: To evaluate the safety, tolerability, and preliminary efficacy of QT-219C in subjects with B-cell-related autoimmune diseases, and to determine the Dose-Limiting Toxicities (DLTs). * Secondary Objective: To characterize the pharmacokinetics (PK, e.g., transgene copy numbers) and pharmacodynamics (PD, e.g., cytokine levels and B-cell depletion) of QT-219C. * Exploratory Objective: To explore correlations between baseline status (e.g., NK cell phenotype), PK/PD, safety, and efficacy, as well as the impact on growth and development (Tanner stage) in pediatric subjects. * 3\. Study Design and Dose Escalation This is an open-label, single-arm, dose-escalation, and expansion study. Dose Escalation: A standard "3+3" design is employed, with an estimated 6-15 subjects in this phase. * Enrollment Priority: Enrollment will prioritize older pediatric subjects. * 4\. Clinical Procedures * Screening (Day -28 to -5): Subjects provide informed consent and undergo baseline laboratory and imaging assessments. * Conditioning (Day -5 to -3): Subjects receive a lymphodepletion regimen. * Infusion (Day 0): Upon confirming adequate organ function and absence of active infection, a single intravenous dose of QT-219C is administered. * DLT Observation (Day 0 to 28): Subjects are closely monitored for 28 days post-infusion to assess hematologic and non-hematologic toxicities. * 5\. Follow-up and Efficacy Evaluation * Safety Management: Intensive monitoring for Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), GvHD, infections, and viral reactivation . * Efficacy Assessment: Evaluations are conducted at Days 28, 60, 90, and 180, with Day 90 and Day 180 serving as key clinical efficacy time points. * Long-term Follow-up: Starting six months post-infusion, subjects enter a long-term follow-up phase with visits every 3 months for up to 2 years or as clinically indicated.