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

Gallagher, Stephen; Turman, Sean; Yusuf, Isharat; Akhgar, Ahmad; Wu, Yuling; Roskos, Lorin; Herbst, Ronald; Wang, Yue

doi:10.1016/j.intimp.2016.04.035

Cited by 14 publications

(15 citation statements)

References 38 publications

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“…Consistent with the preceding in vitro studies, treatment with CD19-2 (the fucosylated version of inebilizumab) also resulted in B-cell depletion but with reduced efficacy than inebilizumab [48]. Both intravenous and subcutaneous administration of inebilizumab showed comparable efficacy, and its pharmacokinetic profile was similar to those of other human IgG1 mAbs in mice [48]. …”

Section: Rationale For Targeting Cd19 and The Development Of Inebisupporting

confidence: 64%

“…We have demonstrated that inebilizumab administration in hCD19 Tg mice leads to dose-dependent depletion of B cells in blood and lymphoid tissues: after a 1-week treatment with inebilizumab at doses of ≥0.5 mg/kg, more than 90% of B cells in spleen, bone marrow, and blood were depleted [48]. Consistent with the preceding in vitro studies, treatment with CD19-2 (the fucosylated version of inebilizumab) also resulted in B-cell depletion but with reduced efficacy than inebilizumab [48].…”

Section: Rationale For Targeting Cd19 and The Development Of Inebimentioning

confidence: 99%

“…Third, the duration of depletion was longer after inebilizumab treatment than after rituximab treatment, probably because inebilizumab is able to deplete early progenitor B cells in bone marrow in hCD19/20 Tg mice. Combined treatment with inebilizumab and rituximab further prolonged B-cell depletion, indicating dual B-cell-depleting therapies can potentially work synergistically [48]. …”

Section: Rationale For Targeting Cd19 and The Development Of Inebimentioning

confidence: 99%

See 2 more Smart Citations

Inebilizumab, a B Cell-Depleting Anti-CD19 Antibody for the Treatment of Autoimmune Neurological Diseases: Insights from Preclinical Studies

Chen

Gallagher²,

Monson

et al. 2016

JCM

Self Cite

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Exaggerated or inappropriate responses by B cells are an important feature in many types of autoimmune neurological diseases. The recent success of B-cell depletion in the treatment of multiple sclerosis (MS) has stimulated the development of novel B-cell-targeting therapies with the potential for improved efficacy. CD19 has emerged as a promising target for the depletion of B cells as well as CD19-positive plasmablasts and plasma cells. Inebilizumab (MEDI-551), an anti-CD19 antibody with enhanced antibody-dependent cell-mediated cytotoxicity against B cells, is currently being evaluated in MS and neuromyelitis optica. This review discusses the role of B cells in autoimmune neurological disorders, summarizes the development of inebilizumab, and analyzes the recent results for inebilizumab treatment in an autoimmune encephalitis mouse model. The novel insights obtained from these preclinical studies can potentially guide future investigation of inebilizumab in patients.

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Section: Rationale For Targeting Cd19 and The Development Of Inebisupporting

confidence: 64%

Section: Rationale For Targeting Cd19 and The Development Of Inebimentioning

confidence: 99%

Section: Rationale For Targeting Cd19 and The Development Of Inebimentioning

confidence: 99%

See 1 more Smart Citation

Inebilizumab, a B Cell-Depleting Anti-CD19 Antibody for the Treatment of Autoimmune Neurological Diseases: Insights from Preclinical Studies

Chen

Gallagher²,

Monson

et al. 2016

JCM

Self Cite

View full text Add to dashboard Cite

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“… 106 Enhanced B-cell depletion over wild type counterpart in human CD19 transgenic mouse at lower dosesGallagher et al. 129 MDX-1342CD19afucosylatedFUT8 −/− CHO cells (Potelligent® Technology)Dose-dependent enhancement of survival in murine B-cell lymphoma model with Ramos cellsCardarelli et al. 103 Human IgG1 Enhanced B-cell depletion over fucosylated counterpart in cynomolgus monkeys Imgatuzumab /GA201/ RG7160EGFRReduced (∼15%)Coexpression with GnT III and α-ManII in CHO cells (GlycoMAb Technology)Enhanced survival rate over fucosylated counterpart in mouse xenograft models displaying murine FcγRIV and over commercial Cetuximab in mouse xenograft models displaying murine FcγRIV and/or human FcγRIIIA.Gerdes et al.…”

Section: Enhanced Adcc Activities By Afucosylated Antibodies In In VImentioning

confidence: 99%

The “less-is-more” in therapeutic antibodies: Afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity

Pereira

Chan

Lin

et al. 2018

mAbs

267

211

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Therapeutic monoclonal antibodies are the fastest growing class of biological therapeutics for the treatment of various cancers and inflammatory disorders. In cancer immunotherapy, some IgG1 antibodies rely on the Fc-mediated immune effector function, antibody-dependent cellular cytotoxicity (ADCC), as the major mode of action to deplete tumor cells. It is well-known that this effector function is modulated by the N-linked glycosylation in the Fc region of the antibody. In particular, absence of core fucose on the Fc N-glycan has been shown to increase IgG1 Fc binding affinity to the FcγRIIIa present on immune effector cells such as natural killer cells and lead to enhanced ADCC activity. As such, various strategies have focused on producing afucosylated antibodies to improve therapeutic efficacy. This review discusses the relevance of antibody core fucosylation to ADCC, different strategies to produce afucosylated antibodies, and an update of afucosylated antibody drugs currently undergoing clinical trials as well as those that have been approved.

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“…Thus, CD19 depletion is a well-validated treatment option for NMOSD. [21][22][23]26 Further safety studies are needed as long-term CD19 depletion may be associated with an elevated risk of opportunistic infections. 27 Perspective A phase 1 study of ublituximab as an add-on therapy to methylprednisolone in an acute relapse of NMOSD suggests that CD20 depletion is safe in this regime and may improve neurologic outcome.…”

Section: Rituximabmentioning

confidence: 99%

Targeting B cells to modify MS, NMOSD, and MOGAD

Graf

Mareś

Barnett

et al. 2021

Neurol Neuroimmunol Neuroinflamm

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Ocrelizumab, rituximab, ofatumumab, ublituximab, inebilizumab, and evobrutinib are immunotherapies that target various B cell–related proteins. Most of these treatments have proven efficacy in relapsing and progressive forms of MS and neuromyelitis optica spectrum disease (NMOSD) or are in advanced stages of clinical development. Currently, ocrelizumab and inebilizumab are licensed for treatment of MS and NMOSD, respectively. This part of the review focuses on monoclonal antibody B cell–depleting strategies in NMOSD and the emerging related myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G–associated disease (MOGAD). Case series and phase 2/3 studies in these inflammatory disorders are assessed. The safety profile of long-term B-cell depletion in MS, NMOSD, and MOGAD will be highlighted. Finally implications of the current coronavirus disease 2019 pandemic on the management of patients with these disorders and the use of B cell–depleting agents will be discussed.

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

Cited by 14 publications

References 38 publications

Inebilizumab, a B Cell-Depleting Anti-CD19 Antibody for the Treatment of Autoimmune Neurological Diseases: Insights from Preclinical Studies

Inebilizumab, a B Cell-Depleting Anti-CD19 Antibody for the Treatment of Autoimmune Neurological Diseases: Insights from Preclinical Studies

The “less-is-more” in therapeutic antibodies: Afucosylated anti-cancer antibodies with enhanced antibody-dependent cellular cytotoxicity

Targeting B cells to modify MS, NMOSD, and MOGAD

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