Action and resistance of monoclonal CD20 antibodies therapy in B-cell Non-Hodgkin Lymphomas

Pérez-Callejo, David; González-Rincón, Julia; Sánchez, Antonio; Provencio, Mariano; Sánchez‐Beato, Margarita

doi:10.1016/j.ctrv.2015.05.007

Cited by 46 publications

(29 citation statements)

References 117 publications

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“…Rituximab is a chimeric monoclonal antibody specifically directed to the transmembrane protein CD20 on B-lymphocytes [1, 2]. It was first introduced in 1997 for the treatment of B cell lymphoma (four weekly doses of 375 mg/m 2 ) [3] and in 2006 it was approved for the treatment of rheumatoid arthritis [4]. In recent years, several studies have shown the efficacy of rituximab in improving the outcome of renal diseases associated with an autoimmune pathology, but the mechanism of action in these diseases is still unclear [5].…”

Section: Introductionmentioning

confidence: 99%

Treatment with rituximab in idiopathic membranous nephropathy

et al. 2016

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BackgroundRituximab represents a valid therapeutic option to induce remission in patients with primary glomerulonephritis. Despite several studies proving its efficacy in improving outcomes in patients with membranous nephropathy (MN), its role in therapeutic protocols is not yet defined.MethodsWe studied 38 patients with idiopathic MN treated with rituximab (in 13 patients as first-line therapy, in the remaining 25 after conventional immunosuppressive therapy). The patients were analyzed for a 15-month median (interquartile range 7.7–30.2) follow-up, with serial monitoring of 24-h proteinuria, renal function and circulating CD19+ B cells.ResultsThe percentages of patients who achieved complete remission, partial remission and the composite endpoint (complete or partial remission) were 39.5% (15 patients), 36.8% (14 patients) and 76.3% (29 patients), respectively. The 24-h proteinuria was reduced significantly during the entire period of follow-up (from a baseline value of 6.1 to 0.9 g/day in the last visit; P < 0.01), while albuminemia increased constantly (from a baseline value of 2.6 to 3.5 g/dL in the last observation; P < 0.01). Renal function did not significantly change during the observation period. Circulating CD19+ B cells were reduced significantly from the baseline value to the 24-month value (P < 0.01); data about anti-phospholipase A2 receptor antibodies were available in 14 patients, 10 of which experienced a decreasing trend after treatment. No significant adverse events were described during and after infusions.ConclusionsThe present study confirmed that treatment with rituximab was remarkably safe and allowed for a large percentage of complete or partial remissions in patients with MN.

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Section: Introductionmentioning

confidence: 99%

Treatment with rituximab in idiopathic membranous nephropathy

et al. 2016

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“…Analysis of the glycosylation of the Fc found that the absence of a bisecting fucose in the Asn297-linked carbohydrate greatly increased interaction of the Fc with FcγRIIIa [120][121][122][123]. Thus, therapeutic Abs that lack this fucose have been shown to have improved receptor binding and target killing functions [124,125], although mechanisms for improved antitumour outcomes in the clinic are multifactorial [126].…”

Section: The Influence Of Igg-fc Glycosylation On Fcγr-mediated Functionmentioning

confidence: 99%

Antibody functional assays as measures of Fc receptor-mediated immunity to HIV - new technologies and their impact on the HIV vaccine field.

Wines¹,

Billings²,

Mcleand³

et al. 2017

CHR

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Background:There is now intense interest in the role of HIV-specific antibodies and the engagement of FcγR functions in the control and prevention of HIV infection. The analyses of the RV144 vaccine trial, natural progression cohorts, and macaque models all point to a role for Fc-dependent effector functions, such as cytotoxicity (ADCC) or phagocytosis (ADCP), in the control of HIV. However, reliable assays that can be reproducibly used across different laboratories to measure Fcdependent functions, such as antibody dependent cellular cytotoxicity (ADCC) are limited. Method: This brief review highlights the importance of Fc properties for immunity to HIV, particularly via FcγR diversity and function. We discuss assays used to study FcR mediated functions of HIV-specific Ab, including our recently developed novel cell-free ELISA using homo-dimeric FcγR ectodomains to detect functionally relevant viral antigen-specific antibodies. Results: The binding of these dimeric FcγR ectodomains, to closely spaced pairs of IgG Fc, mimics the engagement and cross-linking of Fc receptors by IgG opsonized virions or infected cells as the essential prerequisite to the induction of Ab-dependent effector functions. The dimeric FcγR ELISA reliably correlates with ADCC in patient responses to influenza. The assay is amenable to high throughput and could be standardized across laboratories. Conclusion: We propose the assay has broader implications for the evaluation of the quality of antibody responses in viral infections and for the rapid evaluation of responses in vaccine development campaigns for HIV and other viral infections.

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“…However, many patients fail to respond for a variety of reasons. Rituximab, a chimeric mAb composed of human IgG1 constant regions and murine variable regions, is thought to work by three mechanisms: (i) direct signaling and activation of internal apoptotic pathways, (ii) induction of antibody-dependent cell-mediated cytotoxicity (ADCC), and (iii) induction of complement-dependent cytotoxicity (CDC) [1–3]. …”

Section: Introductionmentioning

confidence: 99%

Enhanced CDC of B cell chronic lymphocytic leukemia cells mediated by rituximab combined with a novel anti-complement factor H antibody

et al. 2017

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Rituximab therapy for B cell chronic lymphocytic leukemia (B-CLL) has met with mixed success. Among several factors to which resistance can be attributed is failure to activate complement dependent cytotoxicity (CDC) due to protective complement regulatory proteins, including the soluble regulator complement factor H (CFH). We hypothesized that rituximab killing of non-responsive B-CLL cells could be augmented by a novel human monoclonal antibody against CFH. The B cells from 11 patients with B-CLL were tested ex vivo in CDC assays with combinations of CFH monoclonal antibody, rituximab, and a negative control antibody. CDC of rituximab non-responsive malignant B cells from CLL patients could in some cases be augmented by the CFH monoclonal antibody. Antibody-mediated cytotoxicity of cells was dependent upon functional complement. In one case where B-CLL cells were refractory to CDC by the combination of rituximab plus CFH monoclonal antibody, additionally neutralizing the membrane complement regulatory protein CD59 allowed CDC to occur. Inhibiting CDC regulatory proteins such as CFH holds promise for overcoming resistance to rituximab therapy in B-CLL.

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Action and resistance of monoclonal CD20 antibodies therapy in B-cell Non-Hodgkin Lymphomas

Cited by 46 publications

References 117 publications

Treatment with rituximab in idiopathic membranous nephropathy

Treatment with rituximab in idiopathic membranous nephropathy

Antibody functional assays as measures of Fc receptor-mediated immunity to HIV - new technologies and their impact on the HIV vaccine field.

Enhanced CDC of B cell chronic lymphocytic leukemia cells mediated by rituximab combined with a novel anti-complement factor H antibody

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