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Updated: Oct 21, 2025
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A Syngeneic Mouse B-Cell Lymphoma Model for Pre-Clinical Evaluation of CD19 CAR T Cells
Published on: October 16, 2018
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A novel and efficient tandem CD19- and CD22-directed CAR for B cell ALL
Samanta Romina Zanetti1, Talia Velasco-Hernandez2, Francisco Gutierrez-Agüera2
1Josep Carreras Leukemia Research Institute, School of Medicine, University of Barcelona, Carrer Casanova 143, 4° floor, Barcelona 08036, Spain.
Molecular Therapy : the Journal of the American Society of Gene Therapy
|September 3, 2021
Summary
A novel tandem chimeric antigen receptor (CAR) T-cell therapy targeting both CD19 and CD22 shows promise in overcoming relapse in B cell acute lymphoblastic leukemia (B-ALL). This dual-targeting approach may improve remission rates and reduce antigen loss in B-ALL patients.
Area of Science:
- Immunotherapy
- Oncology
- Cellular Therapy
Background:
- Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has shown efficacy in B cell acute lymphoblastic leukemia (B-ALL).
- Relapse remains a significant challenge due to antigen loss (CD19-negative clones) or CAR T-cell persistence issues.
- CD22 is a pan-B cell marker expressed on both CD19-positive and CD19-negative B-ALL cells, presenting a potential alternative or complementary target.
Purpose of the Study:
- To develop and validate a novel tandem CAR (Tan-CAR) construct targeting both CD19 and CD22 simultaneously.
- To assess the efficacy and safety of the CD22/CD19 Tan-CAR T-cells in preclinical models of B-ALL.
- To evaluate the potential of Tan-CAR therapy to overcome antigen escape mechanisms and improve long-term remission rates.
Main Methods:
- Generation of a 4-1BB-based CD22/CD19 Tan-CAR using novel single-chain variable fragments (scFvs).
- Functional validation using in vitro assays, including assessment of T-cell expansion, tonic signaling, and bispecificity against CRISPR-Cas9-edited B-ALL cells.
- In vivo efficacy studies using B-ALL cell lines, patient samples, and patient-derived xenograft (PDX) models.
Main Results:
- The generated Tan-CAR T-cells exhibited similar in vitro expansion to CD19-CAR T-cells without increased tonic signaling.
- CRISPR-Cas9 editing confirmed the bispecific targeting capability of the Tan-CAR.
- Tan-CAR demonstrated comparable in vitro and in vivo anti-leukemic activity to CD19-CAR, with a trend towards superior disease control in long-term PDX models.
- The robust anti-leukemic activity of the Tan-CAR was effective in controlling disease in long-term follow-up PDX models.
Conclusions:
- The novel CD22/CD19 Tan-CAR T-cell construct is functionally validated and shows potent anti-leukemic activity in preclinical B-ALL models.
- Simultaneous targeting of CD19 and CD22 offers a potential strategy to overcome antigen loss and reduce relapse rates in B-ALL.
- This Tan-CAR warrants clinical investigation to determine its efficacy in enhancing leukemia eradication and improving outcomes for B-ALL patients.
