Core Viewpoint - The article discusses the promising efficacy of CAR-T cell therapy in treating relapsed or refractory multiple myeloma, highlighting the transition from traditional autologous CAR-T to in vivo CAR-T approaches, which simplify the manufacturing process and reduce costs [2][3][4]. Group 1: In Vivo CAR-T Therapy - In vivo CAR-T therapy involves directly delivering CAR transgenes to endogenous T cells within the body, eliminating the need for complex manufacturing and storage processes associated with traditional CAR-T therapies [3][4]. - A clinical study published in The Lancet reported the first human trial data for in vivo CAR-T therapy targeting B-cell maturation antigen (BCMA) in multiple myeloma patients, demonstrating effective treatment in four patients [4][18]. Group 2: ESO-T01 Development - ESO-T01 is a novel lentiviral vector designed for in vivo T cell engineering, developed by EsoBiotec and Prigen, featuring a humanized single-domain antibody CAR targeting BCMA [6][9]. - The vector has been engineered to reduce immunogenicity and enhance specificity, including mutations to the VSVG protein and overexpression of CD47 to evade the immune system [6]. Group 3: Clinical Trial Results - The ongoing Phase 1 trial involved four adult patients with relapsed or refractory multiple myeloma, all of whom had previously shown disease progression despite multiple treatments [9][10]. - Initial dosing of ESO-T01 was set at 2.0×10^8 transduction units, with all patients experiencing acute inflammatory responses post-infusion, including fever and low blood pressure [11][13]. - By the end of the two-month follow-up, two patients achieved stringent complete responses, while the other two showed partial responses with tumor shrinkage [12][14]. Group 4: Safety and Efficacy Observations - The trial noted significant hematological toxicities, including neutropenia and thrombocytopenia, but most adverse effects resolved during follow-up [13]. - The presence of CAR-T cells was first detected in peripheral blood between days 4-8 post-infusion, peaking between days 10-17, indicating effective T cell expansion [14][18]. - The study provides valuable data for future research on in vivo CAR-T therapies, emphasizing the potential of ESO-T01 in treating difficult-to-manage multiple myeloma cases [19].