STTT：隗佳/张义成/周晓曦团队揭示，双靶点CAR-T细胞疗法具有治愈TP53突变癌症的潜力

Core Viewpoint - The study highlights the potential curative effects of dual CD19/CD22 CAR-T cell therapy, either alone or in combination with autologous stem cell transplantation (ASCT), for patients with TP53 gene mutations in relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL) [5][9]. Summary by Sections TP53 Gene and Its Importance - The TP53 gene is a crucial tumor suppressor gene, often referred to as the "guardian of the genome," playing a significant role in maintaining genomic stability through various cellular processes [2]. Prevalence of TP53 Mutations in r/r B-NHL - In r/r B-NHL, particularly in diffuse large B-cell lymphoma (DLBCL), the mutation rate of the TP53 gene ranges from 30% to 63%, correlating with treatment resistance and poorer overall survival and progression-free survival [3]. CAR-T Cell Therapy and Its Efficacy - CD19-targeted CAR-T cell therapy has emerged as a vital second-line treatment for r/r B-NHL, offering the possibility of sustained remission, although its effectiveness in patients with TP53 mutations remains debated [3][6]. Research Findings - A recent study reported long-term follow-up results for 122 r/r B-NHL patients, with a median follow-up of 77.77 months, showing no significant differences in overall survival (OS) and progression-free survival (PFS) between TP53 mutation carriers and wild-type patients [6][8]. Treatment Outcomes - Sequential ASCT followed by CAR-T cell therapy (Group B) demonstrated improved 5-year OS (70.2% vs 40.0%) and PFS (64.9% vs 35.4%) compared to CAR-T therapy alone (Group A) [8]. - The overall 5-year cumulative non-relapse mortality rate was 10.7%, with a secondary malignancy occurrence in 2.5% of patients and a severe infection rate of 13.6% post-treatment [8]. Conclusion on Treatment Implications - The findings suggest that dual-target CAR-T cell therapy, especially when combined with ASCT, may mitigate the adverse prognostic impact of TP53 mutations, providing sustained clinical benefits in r/r B-NHL while maintaining manageable long-term toxicity [9].