BangBio Announces Positive Results from Allogeneic Universal CAR-T Therapy TyU19 in Refractory Systemic Lupus Erythematosus

May 14, 2025 11:21 CST Updated 11:21

BRL Medicine

Cell and Gene Therapy Drug Developer

May 13,BRL Medicine Announces, International Academic JournalCell ResearchRecentlyPublication of a clinical research paper reporting the use of allogeneic anti-CD19 CAR-T cells (TyU19) edited by CRISPR/Cas9 gene editing to treat relapsed/refractory systemic lupus erythematosus (SLE).The study results show that TyU19 cells can achieve rapid and deep clinical remission in SLE treatment, while demonstrating excellent clinical safety.

2025年5月8日，Cell Research发文（https://doi.org/10.1038/s41422-025-01128-1）

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by abnormal B-cell activation and the production of autoantibodies, with traditional immunosuppressants showing limited efficacy in some patients. Autologous CAR-T therapy has achieved initial success in SLE but is limited by the long individualized preparation cycle and high costs. Allogeneic CAR-T cells offer advantages such as homogeneity and immediate availability; however, challenges like graft-versus-host disease (GVHD), host rejection, gene-editing-related genotoxicity risks, and infection risks due to excessive immune suppression have also restricted their widespread clinical application.

In this investigator-initiated clinical study (IIT), the research team evaluatedTyU19Safety and Efficacy in Refractory Systemic Lupus Erythematosus.TyU19, developed by BRL Medicine, mainly utilizes healthy donor cells and employs a multi-gene, selective gene editing strategy to perform multiple precise edits on donor T cells (knocking out the TRAC, HLA-A, HLA-B, CIITA, and PD-1 genes) to fundamentally eliminate the risk of host rejection and GVHD.

From September 2023 to September 2024, the study enrolled four female patients aged 22-24 years with relapsing/refractory SLE. Their baseline SELENA-SLEDAI scores ranged from 14 to 26, all with a history of multi-system involvement (some had a previous history of lupus encephalitis) and were unresponsive to conventional immunosuppressants and biologics.All patients receivedAfter TyU19 cell infusion treatment, the clinical results showed:

In terms of efficacy: All patients reached the SRI-4 sustained response criteria within 3 months, showing continuous improvement in clinical signs and symptoms. Between 3 to 6 months, the SELENA-SLEDAI disease activity score dropped to 0, with complete remission of clinical symptoms such as arthritis, alopecia, and vasculitis; complement levels and key antibody indicators returned to normal.

Immune Remodeling:All patients achieved deep B-cell depletion within one week after infusion, with abnormal B-cell activation being profoundly suppressed. The proportion of memory B cells and plasma cells—the main culprits behind autoantibody production—decreased significantly., suggesting that TyU19 may suppress autoantibody production by remodeling B-cell homeostasis;

In terms of safety, all patients only experienced grade 1 cytokine release syndrome (CRS, transient fever), and during the treatment period, no patients developed immune effector cell-associated neurotoxicity syndrome (ICANS) or graft-versus-host disease (GVHD). The grade 3-4 adverse events were mainly neutropenia and lymphopenia, with no severe infections occurring.

BRL Medicine's press release stated,In this clinical trial, one patient discontinued all hormones and immunosuppressive drugs after TyU19 cell therapy and achieved drug-free remission.This not only suggests that allogeneic CAR-T could become a highly promising treatment for SLE patients who are unresponsive to traditional therapies, but this study also lays an important clinical foundation for the use of allogeneic CAR-T in treating autoimmune diseases, potentially establishing a new paradigm for autoimmune treatment.

References:
[1] World's first: BRL Medicine's allogeneic universal CAR-T cell successfully treats relapsed/refractory systemic lupus erythematosus. From https://www.prnasia.com/story/488732-1.shtml

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