Preclinical efficacy of daratumumab in T-cell acute lymphoblastic leukemia.
Blood
; 131(9): 995-999, 2018 03 01.
Article
em En
| MEDLINE
| ID: mdl-29305553
As a consequence of acquired or intrinsic disease resistance, the prognosis for patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) is dismal. Novel, less toxic drugs are clearly needed. One of the most promising emerging therapeutic strategies for cancer treatment is targeted immunotherapy. Immune therapies have improved outcomes for patients with other hematologic malignancies including B-cell ALL; however no immune therapy has been successfully developed for T-ALL. We hypothesize targeting CD38 will be effective against T-ALL. We demonstrate that blasts from patients with T-ALL have robust surface CD38 surface expression and that this expression remains stable after exposure to multiagent chemotherapy. CD38 is expressed at very low levels on normal lymphoid and myeloid cells and on a few tissues of nonhematopoietic origin, suggesting that CD38 may be an ideal target. Daratumumab is a human immunoglobulin G1κ monoclonal antibody that binds CD38, and has been demonstrated to be safe and effective in patients with refractory multiple myeloma. We tested daratumumab in a large panel of T-ALL patient-derived xenografts (PDX) and found striking efficacy in 14 of 15 different PDX. These data suggest that daratumumab is a promising novel therapy for pediatric T-ALL patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas de Membrana
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ADP-Ribosil Ciclase 1
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Leucemia-Linfoma Linfoblástico de Células T Precursoras
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Anticorpos Monoclonais
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Proteínas de Neoplasias
Limite:
Adolescent
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Adult
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Animals
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Revista:
Blood
Ano de publicação:
2018
Tipo de documento:
Article
País de publicação:
Estados Unidos