The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial
Open accessAbstract
Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Ten of 16 patients with large B cell lymphoma (LBCL) with progressive disease after CAR19 treatment had absent or low CD19. Lower surface CD19 density pretreatment was associated with progressive disease. To prevent relapse with CD19− or CD19 lo disease, we tested a bispecific CAR targeting CD19 and/or CD22 (CD19-22.BB.z-CAR) in a phase I clinical trial (NCT03233854) of adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) and LBCL. The primary end points were manufacturing feasibility and safety with a secondary efficacy end point. Primary end points were met; 97% of products met protocol-specified dose and no dose-limiting toxicities occurred during dose escalation. In B-ALL (n = 17), 100% of patients responded with 88% minimal residual disease-negative complete remission (CR); in LBCL (n = 21), 62% of patients responded with 29% CR. Relapses were CD19−/lo in 50% (5 out of 10) of patients with B-ALL and 29% (4 out of 14) of patients with LBCL but were not associated with CD22−/lo disease. CD19/22-CAR products demonstrated reduced cytokine production when stimulated with CD22 versus CD19. Our results further implicate antigen loss as a major cause of CAR T cell resistance, highlight the challenge of engineering multi-specific CAR T cells with equivalent potency across targets and identify cytokine production as an important quality indicator for CAR T cell potency.
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Citations
Cites
Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma
Neelapu, S. S., Locke, F. L., Bartlett, N. L., Lekakis, L. J., Miklos, D. B., Jacobson, C. A., Braunschweig, I., Oluwole, O. O., Siddiqi, T., Lin, Y., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1707447 · Cited by 6,030
Self-citationTisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia
Maude, S. L., Laetsch, T. W., Buechner, J., Rives, S., Boyer, M., Bittencourt, H., Bader, P., Verneris, M. R., Stefanski, H. E., Myers, G. D., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1709866 · Cited by 5,735
Self-citationCheson, B. D., Fisher, R. I., Barrington, S. F., Cavalli, F., Schwartz, L. H., Zucca, E., & Lister, T. A. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.54.8800 · Cited by 5,715
Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Schuster, S. J., Bishop, M. R., Tam, C. S., Waller, E. K., Borchmann, P., McGuirk, J. P., Jäger, U., Jaglowski, S., Andreadis, C., Westin, J. R., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1804980 · Cited by 4,112
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Self-citationCurrent concepts in the diagnosis and management of cytokine release syndrome.
Lee, D. W., Gardner, R., Porter, D. L., Louis, C. U., Ahmed, N., Jensen, M., Grupp, S. A., & Mackall, C. L. (2014) · Blood · doi:10.1182/blood-2014-05-552729 · Cited by 2,806
Self-citationLong-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia
Park, J. H., Rivière, I., Gonen, M., Wang, X., Sénéchal, B., Curran, K. J., Sauter, C., Wang, Y., Santomasso, B., Mead, E., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1709919 · Cited by 2,688
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Locke, F. L., Ghobadi, A., Jacobson, C. A., Miklos, D. B., Lekakis, L. J., Oluwole, O. O., Lin, Y., Braunschweig, I., Hill, B. T., Timmerman, J. M., et al. (2019) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30864-7 · Cited by 2,286
Self-citation
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
Exploring treatment options in cancer: tumor treatment strategies
Liu, B., Zhou, H., Tan, L., Siu, K. T. H., & Guan, X.-Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01856-7 · Cited by 1,201
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
Self-citationCordoba, S., Onuoha, S., Thomas, S., Pignataro, D. S., Hough, R., Ghorashian, S., Vora, A., Bonney, D., Veys, P., Rao, K., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01497-1 · Cited by 285
A bispecific CAR-T cell therapy targeting BCMA and CD38 in relapsed or refractory multiple myeloma
Mei, H., Li, C., Jiang, H., Zhao, X., Huang, Z., Jin, D., Guo, T., Kou, H., Liu, L., Tang, L., et al. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01170-7 · Cited by 222
Metadata
- Authors
- Spiegel, J. Y., Patel, S., Muffly, L., Hossain, N. M., Oak, J., Baird, J. H., Frank, M. J., Shiraz, P., Sahaf, B., Craig, J., Iglesias, M., Younes, S., Natkunam, Y., Ozawa, M. G., Yang, E., Tamaresis, J., Chinnasamy, H., Ehlinger, Z., Reynolds, W., Lynn, R., Rotiroti, M. C., Gkitsas, N., Arai, S., Johnston, L., Lowsky, R., Majzner, R. G., Meyer, E., Negrin, R. S., Rezvani, A. R., Sidana, S., Shizuru, J., Weng, W.-K., Mullins, C., Jacob, A., Kirsch, I., Bazzano, M., Zhou, J., Mackay, S., Bornheimer, S. J., Schultz, L., Ramakrishna, S., Davis, K. L., Kong, K. A., Shah, N. N., Qin, H., Fry, T., Feldman, S., Mackall, C. L., & Miklos, D. B.
- Venue
- Nature Medicine
- Published
- 2021-07-26
- Volume
- 27
- Issue
- 8
- Pages
- 1419-1431
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W3183792933
- Cited by
- 606
- References
- 70
- FWCI
- 31.96
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Spiegel, J. Y., Patel, S., Muffly, L., Hossain, N. M., Oak, J., Baird, J. H., Frank, M. J., Shiraz, P., Sahaf, B., Craig, J., Iglesias, M., Younes, S., Natkunam, Y., Ozawa, M. G., Yang, E., Tamaresis, J., Chinnasamy, H., Ehlinger, Z., Reynolds, W., . . . Miklos, D. B. (2021). CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nature Medicine. https://doi.org/10.1038/s41591-021-01436-0
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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