Abstract
The outcome for patients with refractory or relapsed acute lymphoblastic leukemia (ALL) treated with conventional therapy is poor. Immunoconjugates present a novel approach and have recently been shown to have efficacy in this setting. Combotox is a mixture of two ricin-conjugated monoclonal antibodies (RFB4 and HD37) directed against CD19 and CD22, respectively, and has shown activity in pediatric and adult ALL. We created a murine xenograft model of advanced ALL using the NALM/6 cell line to explore whether the combination of Combotox with the cytotoxic agent cytarabine (Ara-C) results in better outcomes. In our model the combination of both low- and high-dose Combotox and Ara-C resulted in significantly longer median survival. Sequential administration of Ara-C and Combotox, however, was shown to be superior to concurrent administration. These findings have led to a phase I clinical trial exploring this combination in adults with relapsed or refractory B-lineage ALL (ClinicalTrials.gov identifier NCT01408160).
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Antibodies, Monoclonal / administration & dosage*
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Antibodies, Monoclonal / chemistry
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / therapeutic use
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Antigens, CD19 / chemistry
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Antigens, CD19 / immunology
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Cell Line, Tumor
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Cytarabine / administration & dosage*
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Disease Models, Animal
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Drug Combinations
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Drug Synergism
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Humans
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Immunotoxins / administration & dosage*
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Mice
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Mice, Inbred NOD
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Neoplasm Staging
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
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Ricin / chemistry
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Ricin / therapeutic use
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Sialic Acid Binding Ig-like Lectin 2 / chemistry
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Sialic Acid Binding Ig-like Lectin 2 / immunology
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Xenograft Model Antitumor Assays
Substances
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Antibodies, Monoclonal
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Antigens, CD19
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Drug Combinations
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Immunotoxins
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Sialic Acid Binding Ig-like Lectin 2
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combotox
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Cytarabine
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Ricin
Associated data
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ClinicalTrials.gov/NCT01408160