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2022-02-02

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cc-by-nc-nd (c) Romecín, Paola Alejandra et al., 2022
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/218503

A novel and efficient tandem CD19- and CD22-directed CAR for B cell ALL

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https://doi.org/10.1016/j.ymthe.2021.08.033

Abstract

CD19-directed chimeric antigen receptor (CAR) T cells have yielded impressive response rates in refractory/relapse B cell acute lymphoblastic leukemia (B-ALL); however, most patients ultimately relapse due to poor CAR T cell persistence or resistance of either CD19+ or CD19- B-ALL clones. CD22 is a pan-B marker whose expression is maintained in both CD19+ and CD19- relapses. CD22-CAR T cells have been clinically used in B-ALL patients, although relapse also occurs. T cells engineered with a tandem CAR (Tan-CAR) containing in a single construct both CD19 and CD22 scFvs may be advantageous in achieving higher remission rates and/or preventing antigen loss. We have generated and functionally validated using cutting-edge assays a 4-1BB-based CD22/CD19 Tan-CAR using in-house-developed novel CD19 and CD22 scFvs. Tan-CAR-expressing T cells showed similar in vitro expansion to CD19-CAR T cells with no increase in tonic signaling. CRISPR-Cas9-edited B-ALL cells confirmed the bispecificity of the Tan-CAR. Tan-CAR was as efficient as CD19-CAR in vitro and in vivo using B-ALL cell lines, patient samples, and patient-derived xenografts (PDXs). Strikingly, the robust antileukemic activity of the Tan-CAR was slightly more effective in controlling the disease in long-term follow-up PDX models. This Tan-CAR construct warrants a clinical appraisal to test whether simultaneous targeting of CD19 and CD22 enhances leukemia eradication and reduces/delays relapse rates and antigen loss.

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Limfòcits, Antígens, Immunoteràpia

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Lymphocytes, Antigens, Immunotheraphy

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ROMECÍN, Paola Alejandra, et al. A novel and efficient tandem CD19- and CD22-directed CAR for B cell ALL. Molecular Therapy. 2022. Vol. 30, num. 2, pags. 550-563. ISSN 1525-0016. [consulted: 13 of August of 2026]. Available at: https://hdl.handle.net/2445/218503

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