Xinfeng Chen1,2, Xin Li2, Yanfen Liu1,2, Zhen Zhang1,2, Xudong Zhang2, Jianmin Huang1, Hong Li1, Feng Li2, Lei Zhang2, Ling Li2, Xiaolong Wu2, Wang Ma2, Zhenchang Sun2, Hui Yu2, Zhiyuan Zhou2, Xiaoyan Feng2, Kang Cui2, Zhaoming Li2, Hongling Zhang3, Ying Zeng3, Xiaochun Wan4, Youhai H Chen5, Mingzhi Zhang2, Yi Zhang1,2,6,7. 1. Biotherapy Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. 2. Cancer Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China. 3. Binde Biotech Inc., Shenzhen 518055, Guangdong, China. 4. Center for Antibody Drug Development, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China. 5. Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. 6. School of Life Sciences, Zhengzhou University, Zhengzhou 450052, Henan, China. 7. Engineering Key Laboratory for Cell Therapy of Henan Province, Zhengzhou 450052, Henan, China.
Abstract
Aim: CD19 chimeric antigen receptor (CAR) T cells have been approved by the US FDA for treatment of relapsed and refractory (R/R) B-cell malignancies. Patients & methods: This study investigated the safety and efficacy of autologous 4-1BB costimulatory domain-engineered CD19 CAR-T cells in R/R B-cell lymphoma. Results: After CD19 CAR-T-cell infusion, severe cytokine release syndrome occurred in 28.6% (4/14) of the patients. The overall response rate was 77% with complete remission observed in 6/14 patients at 3 months. A higher tumor burden and grade 3-4 of myelosuppression after chemotherapy were associated with severe cytokine-release syndrome. Notably, combining CD19 CAR-T cells and PD-1 blockade, but not CD19 CAR-T cells alone, reduced intracranial tumor burden in a patient with central invasion of lymphoma. Conclusion: CD19 CAR-T cells could effectively induce tumor remission and PD-1 blockade might improve the efficacy in Chinese patients with R/R B-cell lymphoma.
Aim: CD19chimeric antigen receptor (CAR) T cells have been approved by the US FDA for treatment of relapsed and refractory (R/R) B-cell malignancies. Patients & methods: This study investigated the safety and efficacy of autologous 4-1BB costimulatory domain-engineered CD19CAR-T cells in R/R B-cell lymphoma. Results: After CD19CAR-T-cell infusion, severe cytokine release syndrome occurred in 28.6% (4/14) of the patients. The overall response rate was 77% with complete remission observed in 6/14 patients at 3 months. A higher tumor burden and grade 3-4 of myelosuppression after chemotherapy were associated with severe cytokine-release syndrome. Notably, combining CD19CAR-T cells and PD-1 blockade, but not CD19CAR-T cells alone, reduced intracranial tumor burden in a patient with central invasion of lymphoma. Conclusion:CD19CAR-T cells could effectively induce tumor remission and PD-1 blockade might improve the efficacy in Chinese patients with R/R B-cell lymphoma.
Entities:
Keywords:
4-1BB; CAR-T cell; CD19; CRS; PD-1; chimeric antigen receptor T cell; cytokine-release syndrome; lymphoma; programmed death 1 receptor; safety
Authors: Oliver Y Tang; Lifeng Tian; Todd Yoder; Rong Xu; Irina Kulikovskaya; Minnal Gupta; Jan Joseph Melenhorst; Simon F Lacey; Donald M O'Rourke; Zev A Binder Journal: Front Immunol Date: 2022-05-06 Impact factor: 8.786