Bispecific CAR-T cells targeting CD19/20 in patients with relapsed or refractory B cell non-Hodgkin lymphoma: a phase I/II trial.
- 2024-08-07
- Blood cancer journal 14(1)
- Lixin Wang
- Chuling Fang
- Qingzheng Kang
- Wenfa Huang
- Ziren Chen
- Weiqiang Zhao
- Lei Wang
- Yiran Wang
- Kun Tan
- Xiao Guo
- Yuanyuan Xu
- Shuhong Wang
- Lijun Wang
- Jingqiao Qiao
- Zhixiong Tang
- Chuan Yu
- Yang Xu
- Yisheng Li
- Li Yu
- PubMed: 39112452
- DOI: 10.1038/s41408-024-01105-8
Study Design
- Type
- Clinical Trial
- Population
- eleven R/R B cell NHL adult patients
- Methods
- Open-label, single-arm trial of autologous CD19/20 CAR-T cells
- Blinding
- Open-label
- Funding
- Unclear
Non-Hodgkin lymphoma (NHL) is a common malignancy in the hematologic system, and traditional therapy has limited efficacy for people with recurrent/refractory NHL (R/R NHL), especially for patients with diffuse large B cell lymphoma (DLBCL). Chimeric antigen receptor (CAR) T-cell therapy is a novel and effective immunotherapy strategy for R/R hematopoietic malignancies, but relapses can occur due to the loss of CAR-T cells in vivo or the loss of antigen. One strategy to avoid antigen loss after CAR-T cell therapy is to target one more antigen simultaneously. Tandem CAR targeting CD19 and CD22 has demonstrated the reliability of tandem CAR-T cell therapy for R/R B-ALL. This study explores the therapeutic potential of tandem CD19/20 CAR-T in the treatment of R/R B cell NHL. The efficacy and safety of autologous CD19/20 CAR-T cells in eleven R/R B cell NHL adult patients were evaluated in an open-label, single-arm trial. Most patients achieved complete response, exhibiting the efficacy and safety of tandem CD19/20 CAR-T cells. The TCR repertoire diversity of CAR-T cells decreased after infusion. The expanded TCR clones in vivo were mainly derived from TCR clones that had increased expression of genes associated with immune-related signaling pathways from the infusion product (IP). The kinetics of CAR-T cells in vivo were linked to an increase in the expression of genes related to immune response and cytolysis/cytotoxicity.