Bispecific CAR-T cells targeting CD19/20 in patients with relapsed or refractory B cell non-Hodgkin lymphoma: a phase I/II trial

Wang，Lixin1,2; Fang，Chuling1; Kang，Qingzheng1; Huang，Wenfa1; Chen，Ziren1; Zhao，Weiqiang1; Wang，Lei1; Wang，Yiran1; Tan，Kun1; Guo，Xiao1; Xu，Yuanyuan1; Wang，Shuhong1; Wang，Lijun1; Qiao，Jingqiao1; Tang，Zhixiong2,3; Yu，Chuan2,3; Xu，Yang4; Li，Yisheng2,3; Yu，Li1,2

2024-12-01

10.1038/s41408-024-01105-8

Blood Cancer Journal   影响因子和分区

2044-5385

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.

SCI

英语

其他

2-s2.0-85200689394

Scopus

1.Department of Hematology and Oncology,Shenzhen University General Hospital,Shenzhen Key Laboratory,Hematology Institution of Shenzhen University,Shenzhen Clinical Research Center for Hematologic Disease,International Cancer Center,Shenzhen University Health Science Center,Shenzhen University,Shenzhen,Xueyuan AVE 1098,518000,China
2.Shenzhen University—Haoshi Cell Therapy Institute,Shenzhen,155 Hong Tian Road, Bao An District,518125,China
3.Shenzhen Haoshi Biotechnology Co,Ltd,Shenzhen,155 Hong Tian Road, Bao An District,518125,China
4.School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China

Wang，Lixin,Fang，Chuling,Kang，Qingzheng,et al. Bispecific CAR-T cells targeting CD19/20 in patients with relapsed or refractory B cell non-Hodgkin lymphoma: a phase I/II trial[J]. Blood Cancer Journal,2024,14(1).

Wang，Lixin.,Fang，Chuling.,Kang，Qingzheng.,Huang，Wenfa.,Chen，Ziren.,...&Yu，Li.(2024).Bispecific CAR-T cells targeting CD19/20 in patients with relapsed or refractory B cell non-Hodgkin lymphoma: a phase I/II trial.Blood Cancer Journal,14(1).

Wang，Lixin,et al."Bispecific CAR-T cells targeting CD19/20 in patients with relapsed or refractory B cell non-Hodgkin lymphoma: a phase I/II trial".Blood Cancer Journal 14.1(2024).