Tafasitamab. Monoclonal antibody targeting CD19, Treatment of B-cell malignancies

2020 ◽  
Vol 45 (9) ◽  
pp. 641
Author(s):  
M. Narkhede ◽  
B.D. Cheson
Keyword(s):  
Monoclonal Antibody ◽  
B Cell ◽  
B Cell Malignancies ◽  
Antibody Targeting

Phase I/II study of MEDI-551, a humanized monoclonal antibody targeting CD19, in subjects with relapsed or refractory advanced B-cell malignancies.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8065-8065 ◽  
Author(s):  
Trishna Goswami ◽  
Andres Forero ◽  
Mehdi Hamadani ◽  
Anne Sonet ◽  
Gregor Verhoef ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Phase I ◽  
B Cell ◽  
Transmembrane Protein ◽  
Single Agent ◽  
Tumor Lysis Syndrome ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
B Cell Malignancies ◽  
Antibody Targeting

8065 Background: Novel B-cell targeting agents, including monoclonal antibodies such as rituximab, are among recent advances in treatment of B-cell malignancies. New approaches are needed for patients progressing after rituximab-based therapies. MEDI-551 is an afucosylated monoclonal antibody targeting CD-19, a B-cell restricted transmembrane protein with enhanced affinity and antibody-dependent cellular cytotoxicity. Methods: Pts with relapsed or refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia, or multiple myeloma received single agent MEDI-551 at dosages ranging from 0.5 mg/kg to 12 mg/kg via intravenous infusion over 28-day cycles; cohorts 1-6 received 0.5, 1, 2, 4, 8, and 12 mg/kg, respectively. Results: 25 pts were enrolled in the phase I portion Jun 2010–Aug 2011. No maximum tolerated dose (MTD) was achieved. Most AEs were grade 1/2 with dose-independent frequency and severity (Table). Six pts had grade 3 toxicities including tumor lysis syndrome, infusion reaction, thrombocytopenia, and neutropenia, or grade 4 neutropenia. No grade 5 AEs were seen. All pts recovered. Three partial responses (PR) and 2 complete responses (CR) were seen in DLBCL and FL pts at 0.5, 4, and 8 mg/kg. Activity included a CR lasting 9 mo. in a FL pt in cohort 1, who is currently being retreated with MEDI-551 on relapse. Conclusions: MEDI-551 demonstrated a safety profile warranting further study and showed no MTD reached at the highest dose studied. Anti-tumor activity is suggested by the responses achieved across dose levels. Phase II is currently enrolling subjects. This study is funded by MedImmune, LLC. [Table: see text]

An IgG1-like bispecific antibody targeting CD52 and CD20 for the treatment of B-cell malignancies

Methods ◽  
2019 ◽  
Vol 154 ◽  
pp. 70-76 ◽  
Author(s):  
Junpeng Qi ◽  
Shih-Shih Chen ◽  
Nicholas Chiorazzi ◽  
Christoph Rader
Keyword(s):  
B Cell ◽  
Bispecific Antibody ◽  
B Cell Malignancies ◽  
Antibody Targeting

scholarly journals A novel anti-CD19 monoclonal antibody (GBR 401) with high killing activity against B cell malignancies

2014 ◽  
Vol 7 (1) ◽  
pp. 33 ◽  
Author(s):  
Caroline S Breton ◽  
Aimable Nahimana ◽  
Dominique Aubry ◽  
Julie Macoin ◽  
Pierre Moretti ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
B Cell ◽  
B Cell Malignancies ◽  
Killing Activity

Diagnostic differentiation of chronic B-cell malignancies using monoclonal antibody L161 (CD1c)

1989 ◽  
Vol 71 (1) ◽  
pp. 43-46 ◽  
Author(s):  
Richard A. Jones ◽  
Peter S. Master ◽  
J. A. Child ◽  
Bryon E. Roberts ◽  
Colin Stephen Scott
Keyword(s):  
Monoclonal Antibody ◽  
B Cell ◽  
B Cell Malignancies ◽  
Diagnostic Differentiation

scholarly journals Fc gamma receptor II (CD32) on malignant B cells influences modulation induced by anti-CD19 monoclonal antibody

Blood ◽  
1994 ◽  
Vol 83 (6) ◽  
pp. 1632-1639
Author(s):  
SF Vervoordeldonk ◽  
PA Merle ◽  
EF van Leeuwen ◽  
CE van der Schoot ◽  
AE von dem Borne ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
B Cells ◽  
B Cell ◽  
Cell Line ◽  
B Cell Malignancies ◽  
Antigenic Modulation ◽  
Fc Gamma Receptor ◽  
Gamma Receptor ◽  
Modulation Rate ◽  
Switch Variant

Antigenic modulation is one of many factors determining the effectiveness of monoclonal antibody (MoAb)-mediated therapy. To select the isotype of a CD19 MoAb most suitable for radioimmunotherapy of patients with B-cell malignancies, we studied the influence of MoAb isotype on modulation, after binding of the MoAb to different cell-line cells. The CD19-IgG1 MoAb was found to induce modulation of CD19 antigens on Daudi cell line cells more rapidly than did its IgG2a switch variant. We provide evidence that this difference in modulation rate is caused by the expression of Fc gamma receptor II (Fc gamma RII) on these cells. Experiments aimed at elucidating the mechanism of Fc gamma RII involvement in modulation induction by CD19-IgG1 showed that Fc gamma RII did not comodulate with CD19 MoAbs. However, cocrosslinking of CD19 and Fc gamma RII with CD19-IgG1 MoAb resulted in enhanced calcium mobilization in Daudi cells. This increased signal induction accompanies the enhanced capping and subsequent modulation of CD19 antigens. Because Fc gamma RII is expressed in varying densities on malignant B cells in all differentiation stages, our results have implications for the MoAb isotype most suitable for use in MoAb-based therapy of patients with B-cell malignancies.

Development of a New Fully Human Anti-CD20 Monoclonal Antibody for the Treatment of B-Cell Malignancies.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2349-2349
Author(s):  
Gadi Gazit Bornstein ◽  
Christophe Queva ◽  
Mohammad Tabrizi ◽  
Anne VanAbbema ◽  
Carlos Chavez ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
B Cell ◽  
Clinical Activity ◽  
Human Antibody ◽  
B Cell Malignancies ◽  
B Lymphoma ◽  
Hodgkin's Lymphomas ◽  
Anti Tumor Activity

Abstract In spite of the widespread use of Rituximab, a chimeric monoclonal antibody with demonstrated efficacy in the treatment of non-Hodgkin’s lymphomas, there is a recognized need to develop fully human antibodies with improved efficacy. Towards this end, using XenoMouse™ technology, a fully human IgG1 monoclonal antibody specific to human CD20 was generated. This antibody, denoted mAb 1.5.3, evoked enhanced pro-apoptotic activity in vitro, as compared to Rituximab, in the Ramos human lymphoma cell line. In addition, mAb 1.5.3 was active in mediating complement dependent cytotoxicity (CDC) and elicited improved antibody-dependent cellular cytotoxicity (ADCC) relative to Rituximab in Ramos, Raji, and Daudi human B-lymphoma lines. To recapitulate various aspects of acquired resistance to Rituximab, as observed in a subpopulation of patients, Rituximab-resistant clones were established from lymphoma lines. Interestingly, mAb 1.5.3 demonstrated superior cytolytic activity against engineered Rituximab-refractory lymphoma clones, as well as across multiple human B-lymphoma and chronic B-cell leukemia lines in an in vitro whole blood assay. Furthermore, mAb 1.5.3 exhibited enhanced anti-tumor activity in Rituximab-sensitive cell lines and -refractory engineered lymphoma clones in vivo. Lastly, mAb 1.5.3 produced a superior B-cell depletion profile in lymph node organs and bone marrow as compared to Rituximab in a primate PD model. In contrast to Rituximab, mAb 1.5.3 is a fully human antibody and is thus anticipated to exhibit a longer serum half-life with minimal immunogenicity following repeated administration. In sum, these results demonstrate the superior anti-tumor activity of mAb 1.5.3 relative to Rituximab and its potential for improved clinical activity in the treatment of B-cell malignancies.

scholarly journals Characterization of a Synovial B Cell–Derived Recombinant Monoclonal Antibody Targeting Stromal Calreticulin in the Rheumatoid Joints

2018 ◽  
Vol 201 (5) ◽  
pp. 1373-1381 ◽  
Author(s):  
Elisa Corsiero ◽  
Lucas Jagemann ◽  
Mauro Perretti ◽  
Costantino Pitzalis ◽  
Michele Bombardieri
Keyword(s):  
Monoclonal Antibody ◽  
B Cell ◽  
Recombinant Monoclonal Antibody ◽  
Antibody Targeting

Antagonist Anti-CD40 Monoclonal Antibody, CHIR-12.12, Inhibits Growth of a Rituximab-Resistant NHL Xenograft Model and Achieves Synergistic Activity When Combined with Ineffective Rituximab.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3281-3281 ◽  
Author(s):  
Li Long ◽  
Xia Tong ◽  
Montesa Patawaran ◽  
Lea Aukerman ◽  
Julie Klinger ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Tumor Growth ◽  
B Cell ◽  
Tumor Cells ◽  
Xenograft Model ◽  
Synergistic Activity ◽  
B Cell Malignancies ◽  
Hodgkin's Lymphomas ◽  
Anti Tumor Activity

Abstract CD40 and CD20 are expressed in several B-cell malignancies and represent attractive targets for therapeutic intervention. The anti-CD20 monoclonal antibody, rituximab, is an approved drug for the treatment of non-Hodgkin’s lymphomas. however, the existence of patients with rituximab-resistant disease limits its clinical utility. We have previously reported that the novel, highly potent, fully human antagonistic anti-CD40 monoclonal antibody, CHIR-12.12, generated from XenoMouse® mice (Abgenix, Inc) has greater anti-tumor activity than rituximab in both rituximab-responsive and rituximab-resistant human NHL models. In this study, we evaluated the potential therapeutic application of combining CHIR-12.12 and rituximab for the treatment of NHL. Namalwa is a Burkitt’s lymphoma cell line that gives rise to aggressive rituximab-resistant tumors when implanted in nude mice. Direct treatment of these tumor cells with CHIR-12.12 or rituximab in culture does not affect cell growth when compared to treatment with an isotype control antibody. Although Namalwa cells express more CD20 than CD40 (average of 10,059 CD20 and 3,138 CD40 molecules per cell respectively, P=0.05), when tested for in vitro ADCC killing using human NK cells as effectors, CHIR-12.12 mediated stronger target cell lysis than rituximab (31.43% vs. 14.15%, P<0.0001). Adding CHIR-12.12 and rituximab together did not enhance the in vitro ADCC killing. When CHIR-12.12 and rituximab were tested in a subcutaneous Namalwa xenograft model, CHIR-12.12 alone caused 60% tumor growth inhibition (P=0.028) whereas rituximab alone at 10 and 20 mg/kg did not inhibit Namalwa tumor growth. When tumor-bearing mice were administered rituximab at 10 mg/kg plus CHIR-12.12 at 5 or 10 mg/kg, synergistic anti-tumor activity was observed in a CHIR-12.12 dose-dependent manner. The mean tumor volume reduction in combination groups is 77% with CHIR-12.12 at 5 mg/kg (P=0.0037) and 83% with CHIR-12.12 at 10 mg/kg (P=0.0018), respectively. The potential interaction between CD40 and CD20 molecules was evaluated in vitro by treating the tumor cells with CHIR-12.12 and assessing the change in CD20 expression and vice versa. The result showed no augmentation of one antigen expression by treating the tumor cells with the other antibody. The mechanism of anti-tumor synergy observed in this combination is under evaluation. Taken together, these data suggest that the combination therapy with anti-CD40 CHIR-12.12 and rituximab has the potential to improve patient outcome in B-cell malignancies co-expressing CD20 and CD40 antigens and support the further development of CHIR-12.12 antibody for treatment of B-cell malignancies.

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