Preclinical study of a glycoengineered anti‐human CD20 antibody in murine models of primary cerebral and intraocular B‐cell lymphomas

2011 ◽  
Vol 89 (s248) ◽  
pp. 0-0
Author(s):  
RYM BAGGA
2013 ◽  
Vol 54 (5) ◽  
pp. 3657 ◽  
Author(s):  
Rym Ben Abdelwahed ◽  
Sabrina Donnou ◽  
Hanane Ouakrim ◽  
Lucile Crozet ◽  
Jérémie Cosette ◽  
...  

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2755-2755
Author(s):  
Sabrina Donnou ◽  
Rym Ben Abdelwahed-Bagga ◽  
Jérémie Cosette ◽  
Hanane Ouakrim ◽  
Lucile Crozet ◽  
...  

Abstract Abstract 2755 Background: Primary Central Nervous lymphomas (PCNSL), that comprise primary cerebral lymphoma (PCL) and primary intraocular lymphoma (PIOL), are typically CD20+ diffuse large B-cell lymphomas that have no detectable disease outside the brain or eye. Rituximab (RTX), an anti-CD20 antibody, has demonstrated encouraging clinical benefit in systemic B-cell lymphomas as well as PCL and PIOL, however, the role of RTX in treatment of PCNSL/PIOL remains controversial, and these highly aggressive malignancies are often incurable with available therapies. Therefore, additional treatment options are needed. Ublituximab (UTX) is a novel, glycoengineered chimeric anti-CD20 monoclonal antibody (mAb) that has a high affinity for FcγRIIIa (CD16) receptors, and therefore greater ADCC activity than RTX (Le Garff-Tavernier et al., 2011). Herein, we assess the antitumor effects of UTX compared to RTX in murine models of PCL and PIOL. Methods: The murine lymphoma B-cell line A20.IIA-GFP-hCD20 (H-2d) was injected into the right cerebral striatum (PCL model) or the vitreous (PIOL model) of adult BALB/c mice (H-2d); 7 days later, single doses of UTX were injected either into the tumor site intracerebrally (PCL) or intravitreously (PIOL), or at distance of the tumor site (intrathecally, PCL). RTX was used as a reference compound. Survival was monitored for injected mice for up to 100 days, and flow cytometric analyses were performed to assess tumor growth and T-cell infiltration. Results: In PCL and PIOL models, single doses of UTX had a marked antitumor effect more pronounced than that obtained with an equivalent dose of RTX. In the PCL model, there was an overall survival (OS) advantage with intracerebral injections of UTX compared to RTX (50% vs. 10%, n=10 in each group, p=0.0028). The reduction in tumor cells was correlated with an increased proportion of CD8+ T cells. Moreover, intrathecal injections of UTX increased OS compared to buffer solution. In the PIOL model, the absolute number of tumor cells analyzed 8 days after treatment had decreased more significantly (p=0.027) with UTX compared to the RTX group. This finding again confirmed the superiority of UTX in this setting. Conclusions: These results confirm that the novel, third-generation mAb, UTX has a sustained and greater antitumor effect than RTX on primary cerebral and intraocular lymphomas when assessed in vivo. Additional experiments evaluating the combination of UTX + methotrexate are ongoing. Clinical trials to evaluate UTX as an innovative therapeutic approach to treat primary cerebral and intraocular B-cell lymphomas are currently being evaluated. Disclosures: Jacquet: LFB Biotechnologies: Employment. Fridman:LFB Biotechnologies: Membership on an entity's Board of Directors or advisory committees. Sportelli:TG Therapeutics, Inc.: Employment, Equity Ownership. Urbain:LFB Biotechnologies: Employment.


2012 ◽  
Vol 18 (14) ◽  
pp. 3803-3811 ◽  
Author(s):  
Luigi Scotto ◽  
Marianna Kruithof-de Julio ◽  
Luca Paoluzzi ◽  
Matko Kalac ◽  
Enrica Marchi ◽  
...  

2009 ◽  
Vol 50 (9) ◽  
pp. 1500-1508 ◽  
Author(s):  
T. Olafsen ◽  
D. Betting ◽  
V. E. Kenanova ◽  
F. B. Salazar ◽  
P. Clarke ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Sabrina Donnou ◽  
Claire Galand ◽  
Valérie Touitou ◽  
Catherine Sautès-Fridman ◽  
Zsuzsanna Fabry ◽  
...  

Human B-cell lymphomas, the fourth most common hematologic malignancy, are currently the subject of extensive research. The limited accessibility of biopsies, the heterogeneity among patients, and the subtypes of lymphomas have necessitated the development of animal models to decipher immune escape mechanisms and design new therapies. Here, we summarize the cell lines and murine models used to study lymphomagenesis, the lymphoma microenvironment, and the efficacy of new therapies. These data allow us to understand the role of the immune system in the fight against tumors. Exploring the advantages and limitations of immunocompetent versus immunodeficient models improves our understanding of the molecular and cellular mechanisms of tumor genesis and development as well as the fundamental processes governing the interaction of tumors and their host tissues. We posit that these basic preclinical investigations will open up new and promising approaches to designing better therapies.


2014 ◽  
Vol 2 (Suppl 3) ◽  
pp. P168
Author(s):  
Maximillian Rosario ◽  
Bai Liu ◽  
Lin Kong ◽  
Stephanie E Schneider ◽  
Emily K Jeng ◽  
...  

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