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Updated: Aug 20, 2025
Manufacturing Chimeric Antigen Receptor CAR T Cells for Adoptive Immunotherapy
Published on: December 17, 2019
CD19/CD20 Bispecific Chimeric Antigen Receptor (CAR) in Naive/Memory T Cells for the Treatment of Relapsed or
Sarah M Larson1,2, Christopher M Walthers3, Brenda Ji3
1Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California.
Abstract:
To address antigen escape and loss of T-cell functionality, we report a phase I clinical trial (NCT04007029) evaluating autologous naive and memory T (TN/MEM) cells engineered to express a bispecific anti-CD19/CD20 chimeric antigen receptor (CAR; CART19/20) for patients with relapsed/refractory non-Hodgkin lymphoma (NHL), with safety as the primary endpoint. Ten patients were treated with 36 × 106 to 165 × 106 CART19/20 cells. No patient experienced neurotoxicity of any grade or over grade 1 cytokine release syndrome. One case of dose-limiting toxicity (persistent cytopenia) was observed. Nine of 10 patients achieved objective response [90% overall response rate (ORR)], with seven achieving complete remission [70% complete responses (CR) rate]. One patient relapsed after 18 months in CR but returned to CR after receiving a second dose of CART19/20 cells. Median progression-free survival was 18 months and median overall survival was not reached with a 17-month median follow-up. In conclusion, CART19/20 TN/MEM cells are safe and effective in patients with relapsed/refractory NHL, with durable responses achieved at low dosage levels.
Significance:
Autologous CD19/CD20 bispecific CAR-T cell therapy generated from TN/MEM cells for patients with NHL is safe (no neurotoxicity, maximum grade 1 cytokine release syndrome) and demonstrates strong efficacy (90% ORR, 70% CR rate) in a first-in-human, phase I dose-escalation trial. This article is highlighted in the In This Issue feature, p. 517.
Insights
Bispecific CAR-T therapy targeting CD19 and CD20 in relapsed/refractory non-Hodgkin lymphoma shows high response rates and safety. This novel approach using naive and memory T cells offers durable remissions with low-dose treatment.
Area of Science:
- Oncology
- Immunotherapy
- Cellular Therapy
Background:
- Antigen escape and T-cell exhaustion are challenges in treating relapsed/refractory non-Hodgkin lymphoma (NHL).
- Existing CAR-T therapies face limitations that necessitate novel approaches.
Purpose of the Study:
- To evaluate the safety and efficacy of autologous naive and memory T (TN/MEM) cells engineered to express a bispecific anti-CD19/CD20 chimeric antigen receptor (CAR; CART19/20).
- To assess CART19/20 therapy in patients with relapsed/refractory NHL in a phase I clinical trial (NCT04007029).
Main Methods:
- A phase I, dose-escalation clinical trial was conducted.
- Ten patients with relapsed/refractory NHL received varying doses of CART19/20 cells derived from TN/MEM cells.
- Safety, including neurotoxicity and cytokine release syndrome (CRS), and efficacy endpoints were monitored.
Main Results:
- No patient experienced neurotoxicity; cytokine release syndrome was limited to grade 1.
- Nine out of ten patients achieved an objective response (90% ORR), with seven achieving complete remission (70% CR rate).
- Median progression-free survival was 18 months; median overall survival was not reached with a 17-month follow-up.
Conclusions:
- Autologous TN/MEM CART19/20 cells are safe and effective for treating relapsed/refractory NHL.
- Durable responses were achieved even at low dosage levels, suggesting potential for improved therapeutic outcomes.
- This bispecific CAR-T cell therapy represents a promising advancement in NHL treatment.
![Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F62334.jpg&w=3840&q=50)
