A Phase I clinical trial of chimeric antigen receptor-modified T cells in patients with relapsed and refractory lymphoma
IMMUNOTHERAPY
Authors: Chen, Xinfeng; Li, Xin; Liu, Yanfen; Zhang, Zhen; Zhang, Xudong; Huang, Jianmin; Li, Hong; Li, Feng; Zhang, Lei; Li, Ling; Wu, Xiaolong; Ma, Wang; Sun, Zhenchang; Yu, Hui; Zhou, Zhiyuan; Feng, Xiaoyan; Cui, Kang; Li, Zhaoming; Zhang, Hongling; Zeng, Ying; Wan, Xiaochun; Chen, Youhai H.; Zhang, Mingzhi; Zhang, Yi
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.
Chimeric Antigen Receptor Therapy: How Are We Driving in Solid Tumors?
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Authors: Greenbaum, Uri; Yalniz, Fevzi F.; Srour, Samer A.; Rezvani, Katayoun; Singh, Harjeet; Olson, Amanda; Blumenschein, George, Jr.; Hong, David S.; Shpall, Elizabeth J.; Kebriaei, Partow
Abstract
Immune effector cell (IEC) therapy is emerging as a promising approach in the field of cancer immunotherapy. Clinical IEC trials, predominantly using chimeric antigen receptor (CAR) T cells, have shown excellent responses in CD19+ B cell malignancies and multiple myeloma. In solid tumors, preclinical data are encouraging, but clinical data are in their infancy, and there are challenges in using CAR T therapy in this setting, including (1) on-target off-tumor toxicity, (2) optimal target identification, (3) effective trafficking into bulky tumor tissue, and (4) resistance to tumor immune evasion mechanisms. Novel techniques and modifications are being explored in both the preclinical and clinical settings, aiming to improve treatment efficacy and address the aforementioned obstacles to successful CAR T therapy in solid tumors. Here we review these challenges in a clinically oriented approach and summarize published clinical trials using CAR T therapy in a variety of solid tumors. (c) 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.
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