- Oral presentation
- Open Access
Treatment of leukemia antigen-loss relapses occurring after CD19-targeted immunotherapies by combination of anti-CD123 and anti-CD19 chimeric antigen receptor T cells
© Ruella et al. 2015
Published: 4 November 2015
Anti-CD19 chimeric antigen receptor T cells (CART19) and bi-specific anti-CD19/CD3 antibodies (blinatumomab) are generating unprecedented complete responses in relapsing/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). However, a subset of patients still relapse and about 30-50% of these relapses are characterized by the loss of detectable CD19 [1–3]. The interleukin-3 receptor alpha, or CD123, was shown to be expressed in several hematologic neoplasms, including acute myeloid leukemia and more recently also B-ALL. The goal of this study was to pre-clinically evaluate the impact of targeting both CD19 and CD123 with chimeric antigen receptor T cells for the treatment and prevention of CD19-negative relapses occurring after CD19-directed therapies [4, 5].
Here we demonstrate that CD123 is expressed in CD19-negative B-ALL relapses occurring after CD19-directed therapies, and that combining CART123 cells with CART19 cells is an effective therapy for the treatment and prevention of antigen-loss relapses in B-ALL murine xenografts.
This work was supported by: the 2014 SITC-EMD Serono Cancer Immunotherapy Clinical Fellowship Award and the Gabrielle's Angel Foundation (PI: Marco Ruella); the University of Pennsylvania-Novartis Research Alliance (PI: Carl H. June).
- Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al: Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014, 371 (16): 1507-1517.PubMedPubMed CentralView ArticleGoogle Scholar
- Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K, et al: Efficacy and Toxicity Management of 19-28z CAR T Cell Therapy in B Cell Acute Lymphoblastic Leukemia. Sci Transl Med. 2014, 6 (224): 224ra25-PubMedPubMed CentralView ArticleGoogle Scholar
- Topp MS, Gokbuget N, Stein AS, Zugmaier G, O'Brien S, Bargou RC, et al: Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015, 16 (1): 57-66.PubMedView ArticleGoogle Scholar
- Liu K, Zhu M, Huang Y, Wei S, Xie J, Xiao Y: CD123 and its potential clinical application in leukemias. Life Sci. 2015, 122: 59-64.PubMedView ArticleGoogle Scholar
- Gill S, Tasian SK, Ruella M, Shestova O, Li Y, Porter DL, et al: Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells. Blood. 2014, 123 (15): 2343-2554.PubMedPubMed CentralView ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.