The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
Clinical responses with T lymphocytes targeting malignancy-associated κ light chains
Open accessAbstract
BACKGROUND: Treatment of B cell malignancies with adoptive transfer of T cells with a CD19-specific chimeric antigen receptor (CAR) shows remarkable clinical efficacy. However, long-term persistence of T cells targeting CD19, a pan-B cell marker, also depletes normal B cells and causes severe hypogammaglobulinemia. Here, we developed a strategy to target B cell malignancies more selectively by taking advantage of B cell light Ig chain restriction. We generated a CAR that is specific for the κ light chain (κ.CAR) and therefore recognizes κ-restricted cells and spares the normal B cells expressing the nontargeted λ light chain, thus potentially minimizing humoral immunity impairment. METHODS: We conducted a phase 1 clinical trial and treated 16 patients with relapsed or refractory κ+ non-Hodgkin lymphoma/chronic lymphocytic leukemia (NHL/CLL) or multiple myeloma (MM) with autologous T cells genetically modified to express κ.CAR (κ.CARTs). Other treatments were discontinued in 11 of the 16 patients at least 4 weeks prior to T cell infusion. Six patients without lymphopenia received 12.5 mg/kg cyclophosphamide 4 days before κ.CART infusion (0.2 × 108 to 2 × 108 κ.CARTs/m2). No other lymphodepletion was used. RESULTS: κ.CART expansion peaked 1-2 weeks after infusion, and cells remained detectable for more than 6 weeks. Of 9 patients with relapsed NHL or CLL, 2 entered complete remission after 2 and 3 infusions of κ.CARTs, and 1 had a partial response. Of 7 patients with MM, 4 had stable disease lasting 2-17 months. No toxicities attributable to κ.CARTs were observed. CONCLUSION: κ.CART infusion is feasible and safe and can lead to complete clinical responses. TRIAL REGISTRATION: ClinicalTrials.gov NCT00881920. FUNDING: National Cancer Institute (NCI) grants 3P50CA126752 and 5P30CA125123 and Leukemia and Lymphoma Society (LLS) Specialized Centers of Research (SCOR) grant 7018.
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Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia
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Chimeric Antigen Receptor–Modified T Cells for Acute Lymphoid Leukemia
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Metadata
- Authors
- Ramos, C. A., Savoldo, B., Torrano, V., Ballard, B., Zhang, H., Dakhova, O., Liu, E., Carrum, G., Kamble, R. T., Gee, A. P., Mei, Z., Wu, M.-F., Liu, H., Grilley, B., Rooney, C. M., Brenner, M. K., Heslop, H. E., & Dotti, G.
- Venue
- Journal of Clinical Investigation
- Published
- 2016-06-06
- Volume
- 126
- Issue
- 7
- Pages
- 2588-2596
- ISSN
- 0021-9738 (ISSN-L)
- 1558-8238
- OpenAlex
- W2413807845
- Cited by
- 276
- References
- 8
- FWCI
- 18.08
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Ramos, C. A., Savoldo, B., Torrano, V., Ballard, B., Zhang, H., Dakhova, O., Liu, E., Carrum, G., Kamble, R. T., Gee, A. P., Mei, Z., Wu, M.-F., Liu, H., Grilley, B., Rooney, C. M., Brenner, M. K., Heslop, H. E., & Dotti, G. (2016). Clinical responses with T lymphocytes targeting malignancy-associated κ light chains. Journal of Clinical Investigation. https://doi.org/10.1172/jci86000
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