Single-cell analysis of refractory anti-SRP necrotizing myopathy treated with anti-BCMA CAR-T cell therapy

• DOI: 10.1073/pnas.2315990121
• Publication Date: 2024-01-30T18:30:15Z
• Authors: Chuan Qin; Ming-Hao Dong; Luo-Qi Zhou; Wen Wang; Song-Bai Cai; Yun-Fan You; Ke Shang; Jun Xiao; Di Wang; Chun-Rui Li; Min Zhang; Bi-Tao Bu; Dai-Shi Tian; Wei Wang
• Keywords: 0303 health sciences; Receptors, Chimeric Antigen; Cell- and Tissue-Based Therapy; Biological Sciences; Immunotherapy, Adoptive; Autoimmune Diseases; 03 medical and health sciences; Muscular Diseases; Neuroinflammatory Diseases; Tumor Microenvironment; Humans; B-Cell Maturation Antigen; Single-Cell Analysis; Multiple Myeloma; Autoantibodies

Immune-mediated necrotizing myopathy (IMNM) is an autoimmune disorder associated with the presence of autoantibodies, characterized by severe clinical presentation rapidly progressive muscular weakness and elevated levels creatine kinase, while traditional pharmacological approaches possess varying often limited effects. Considering pathogenic role chimeric antigen receptor (CAR)-T cells targeting B cell maturation (BCMA) have emerged as a promising therapeutic strategy. We reported here patient anti-signal recognition particle IMNM refractory to multiple available therapies, who was treated BCMA-targeting CAR-T cells, exhibited favorable safety profiles, sustained reduction in persistent improvements over 18 mo. Longitudinal single-cell RNA, receptor, T sequencing analysis presented normalization immune microenvironment after infusion, including reconstitution lineages, replacement subclusters, suppression overactivated cells. Analysis on characteristics demonstrated more active expansion CD8 + dynamic phenotype shifting pattern similar CD4 A comparison patients those malignancies collected at different timepoints revealed NK-like enhanced tendency death neuroinflammation inhibited proliferating ability might be distinct characteristics. Further studies are warranted define molecular features autoimmunity seek higher efficiency longer persistence treating disorders.