Pharmacological profile of MEDI-551, a novel anti-CD19 antibody, in human CD19 transgenic mice.

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Gallagher S, Turman S, Yusuf I, Akhgar A, Wu Y, Roskos LK, Herbst R, Wang Y

Pharmacological profile of MEDI-551, a novel anti-CD19 antibody, in human CD19 transgenic mice.

Int Immunopharmacol. 2016 Jul;36:205-212. doi: 10.1016/j.intimp.2016.04.035. Epub 2016 May 7.

PubMed ID

27163209 [ View in PubMed

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Abstract

B cell depletion therapy is beneficial for patients with B cell malignancies and autoimmune diseases. CD19, a transmembrane protein, is expressed on a vast majority of normal and neoplastic B cells, making it a suitable target for monoclonal antibody (MAb) mediated immunotherapy. We have developed MEDI-551, an affinity optimized and afucosylated IgG1 MAb targeting human CD19 for B cell depletion. MEDI-551 is currently under investigation in multiple clinical trials. Because MEDI-551 does not cross react with rodent and non-human primate CD19, the pharmacological characteristics of the MAb were evaluated in human CD19 transgenic mice (hCD19 Tg). Here we show that MEDI-551 potently depletes tissue and circulating B cells in hCD19 Tg mice and is more efficacious than the anti-CD19 MAb with intact fucose. The length of B cell depletion depends on MEDI-551 dose; and, B cell recovery in the circulation follows stepwise phenotypic maturation. Furthermore, intravenous (IV) and subcutaneous (SC) administration of MEDI-551 results in comparable efficacy. Lastly, the combination of MEDI-551 with the anti-CD20 MAb, rituximab, further prolongs the duration of B cell depletion. In summary, the pharmacological profile of MEDI-551 presented in hCD19 Tg mice supports further testing of MEDI-551 in clinical trials involving B cell malignancies and autoimmune diseases.

DrugBank Data that Cites this Article

Drugs

Inebilizumab

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Inebilizumab	B-lymphocyte antigen CD19	Protein	Humans	Yes	Binder	Details