Preclinical study of Ublituximab, a Glycoengineered anti-human CD20 antibody, in murine models of primary cerebral and intraocular B-cell lymphomas - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Investigative Ophthalmology & Visual Science Année : 2013

Preclinical study of Ublituximab, a Glycoengineered anti-human CD20 antibody, in murine models of primary cerebral and intraocular B-cell lymphomas

R. Ben Abdelwahed
  • Fonction : Auteur
S. Donnou
  • Fonction : Auteur
H. Ouakrim
  • Fonction : Auteur
L. Crozet
  • Fonction : Auteur
I. Tourais
  • Fonction : Auteur
B. Fournes
  • Fonction : Auteur
M. Gillard Bocquet
  • Fonction : Auteur
V. Touitou
  • Fonction : Auteur
M. C. Naud
  • Fonction : Auteur
W. H. Fridman
  • Fonction : Auteur
C. Sautes-Fridman
  • Fonction : Auteur
R. Urbain
  • Fonction : Auteur

Résumé

PURPOSE: Primary cerebral lymphoma (PCL) and primary intraocular lymphoma (PIOL) belong to the systemic diffuse large B-cell lymphoma family and are characterized by the presence of CD20(+) lymphoma B cells in the brain or the eye. These highly aggressive malignancies have a poor prognosis and no specific therapy. The presence of effector immune cells in the damaged brain and vitreous suggests that treatment with anti-human CD20 (hCD20) monoclonal antibodies might be effective. We developed murine models of PCL and PIOL to assess the intracerebral and intraocular antitumor effect of ublituximab, a promising glycoengineered anti-hCD20 mAb with a high affinity for FcgammaRIIIa (CD16) receptors. METHODS: The murine lymphoma B-cell line A20.IIA-GFP-hCD20 (H-2(d)) was injected into the right cerebral striatum or the vitreous of immunocompetent adult BALB/c mice (H-2(d)). Four to 7 days later, ublituximab was injected intracerebrally or intravitreously into the tumor site. Rituximab was the reference compound. Survival was monitored for injected mice; histopathological and flow cytometric analyses were performed to study tumor growth and T-cell infiltration. RESULTS: Single doses of ublituximab, injected intracerebrally or intravitreously, had a marked antitumor effect, more pronounced than that obtained with the same dose of rituximab in these conditions. The reduction in tumor cells was correlated with an increased proportion of CD8(+) T cells. This efficacy was observed only against lymphoma B cells expressing hCD20. CONCLUSIONS: These in vivo results confirm the potential of the glycoengineered anti-hCD20 mAb ublituximab as an innovative therapeutic approach to treat primary central nervous system lymphoma and other B-cell lymphomas.

Dates et versions

hal-02881187 , version 1 (25-06-2020)

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Citer

R. Ben Abdelwahed, S. Donnou, H. Ouakrim, L. Crozet, Jérémie Cosette, et al.. Preclinical study of Ublituximab, a Glycoengineered anti-human CD20 antibody, in murine models of primary cerebral and intraocular B-cell lymphomas. Investigative Ophthalmology & Visual Science, 2013, 54 (5), pp.3657-65. ⟨10.1167/iovs.12-10316⟩. ⟨hal-02881187⟩
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