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A novel antibody-TCR (AbTCR) T-cell therapy is safe and effective against CD19-positive relapsed/refractory B-cell lymphoma.
- Source :
-
Journal of cancer research and clinical oncology [J Cancer Res Clin Oncol] 2023 Jul; Vol. 149 (7), pp. 2757-2769. Date of Electronic Publication: 2022 Jul 01. - Publication Year :
- 2023
-
Abstract
- Purpose: A barrier to widespread adoption of chimeric antigen receptor (CAR) T-cell therapy is toxicity. To address this, we recently developed a novel antibody-T-cell receptor (AbTCR) platform (trademarked as ARTEMIS <superscript>®</superscript> ) which was designed to leverage natural immune receptor signaling and regulation. The AbTCR platform includes a gamma/delta (γδ) TCR-based AbTCR construct and a separate co-stimulatory molecule, both engineered to be tumor-specific. Here, we aim to assess the safety and preliminary efficacy of a CD19-directed AbTCR T-cell therapy.<br />Methods: We generated ET019003 T cells, which are autologous CD19-directed AbTCR T cells. We then conducted an early phase I study to evaluate the safety and preliminary efficacy of ET019003 T cells for the treatment of CD19-positive relapsed/refractory (r/r) B-cell lymphoma.<br />Results: Sixteen patients enrolled in this study and 12 patients were treated. Of the 12 patients treated, 6 patients (50%) achieved a complete response (CR), and 4 (33%) achieved a partial response (PR) (best objective response rate [ORR] of 83%). CRs were durable, including 2 patients with ongoing CRs for 22.7 months and 23.2 months. ET019003 was well-tolerated with an attractive safety profile. No patients experienced severe (grade ≥ 3) cytokine release syndrome (CRS) and only 1 patient experienced immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade. Significant elevations of cytokine levels were not seen, even in patients with marked expansion of ET019003 T cells.<br />Conclusion: This study provides initial clinical validation of the AbTCR platform as a novel cancer treatment with the potential to provide durable clinical benefit with low toxicity.<br />Trial Registration: NCT03642496; Date of registration: August 22, 2018.<br /> (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Details
- Language :
- English
- ISSN :
- 1432-1335
- Volume :
- 149
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Journal of cancer research and clinical oncology
- Publication Type :
- Academic Journal
- Accession number :
- 35776199
- Full Text :
- https://doi.org/10.1007/s00432-022-04132-9