The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial
Open accessAbstract
Chimeric antigen receptor (CAR) T cells targeting CD19 or CD22 have shown remarkable activity in B cell acute lymphoblastic leukemia (B-ALL). The major cause of treatment failure is antigen downregulation or loss. Dual antigen targeting could potentially prevent this, but the clinical safety and efficacy of CAR T cells targeting both CD19 and CD22 remain unclear. We conducted a phase 1 trial in pediatric and young adult patients with relapsed or refractory B-ALL (n = 15) to test AUTO3, autologous transduced T cells expressing both anti-CD19 and anti-CD22 CARs (AMELIA trial, EUDRA CT 2016-004680-39). The primary endpoints were the incidence of grade 3–5 toxicity in the dose-limiting toxicity period and the frequency of dose-limiting toxicities. Secondary endpoints included the rate of morphological remission (complete response or complete response with incomplete bone marrow recovery) with minimal residual disease-negative response, as well as the frequency and severity of adverse events, expansion and persistence of AUTO3, duration of B cell aplasia, and overall and event-free survival. The study endpoints were met. AUTO3 showed a favorable safety profile, with no dose-limiting toxicities or cases of AUTO3-related severe cytokine release syndrome or neurotoxicity reported. At 1 month after treatment the remission rate (that is, complete response or complete response with incomplete bone marrow recovery) was 86% (13 of 15 patients). The 1 year overall and event-free survival rates were 60% and 32%, respectively. Relapses were probably due to limited long-term AUTO3 persistence. Strategies to improve CAR T cell persistence are needed to fully realize the potential of dual targeting CAR T cell therapy in B-ALL.
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Cites
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Self-citationChimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia
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Cited by
Long-term outcomes following CAR T cell therapy: what we know so far
Cappell, K. M., & Kochenderfer, J. N. (2023) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-023-00754-1 · Cited by 1,382
CAR immune cells: design principles, resistance and the next generation
Labanieh, L., & Mackall, C. L. (2023) · Nature · doi:10.1038/s41586-023-05707-3 · Cited by 658
Metadata
- Authors
- Cordoba, S., Onuoha, S., Thomas, S., Pignataro, D. S., Hough, R., Ghorashian, S., Vora, A., Bonney, D., Veys, P., Rao, K., Lucchini, G., Chiesa, R., Chu, J., Clark, L., Fung, M. M., Smith, K., Peticone, C., Al-Hajj, M., Baldan, V., Ferrari, M., Srivastava, S., Jha, R., Arce Vargas, F., Duffy, K., Day, W., Virgo, P., Wheeler, L., Hancock, J., Farzaneh, F., Domning, S., Zhang, Y., Khokhar, N. Z., Peddareddigari, V. G. R., Wynn, R., Pule, M., & Amrolia, P. J.
- Venue
- Nature Medicine
- Published
- 2021-10
- Volume
- 27
- Issue
- 10
- Pages
- 1797-1805
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W3207961322
- Cited by
- 285
- References
- 27
- FWCI
- 15.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Cordoba, S., Onuoha, S., Thomas, S., Pignataro, D. S., Hough, R., Ghorashian, S., Vora, A., Bonney, D., Veys, P., Rao, K., Lucchini, G., Chiesa, R., Chu, J., Clark, L., Fung, M. M., Smith, K., Peticone, C., Al-Hajj, M., Baldan, V., . . . Amrolia, P. J. (2021). CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial. Nature Medicine. https://doi.org/10.1038/s41591-021-01497-1
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
