Search results for " Bispecific"

Test system for trifunctional antibodies in 3D MCTS culture.

2009

The aim of the present study was to assess the feasibility of a 3D tumor cell culture model, that is, multicellular tumor spheroids (MCTSs) as an adequate model for micrometastases and therefore as a pharmacological model for efficacy testing of trifunctional therapeutic antibodies. Unlike conventional monolayer cultures, spheroids allow researchers to study parameters, such as 3D cell shape, 3D cell arrangement and microenvironment, and penetration efficiency of defense cells that may largely influence the efficacy of antibody treatment in vivo. The authors established a long-term coculture of human MCTSs with peripheral blood mononuclear cells (PBMCs) to test the anticancer effect of the …

Therapeutic afucosylated monoclonal antibody and bispecific T-cell engagers for T-cell acute lymphoblastic leukemia

2021

BackgroundT-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with a poor cure rate for relapsed/resistant patients. Due to the lack of T-cell restricted targetable antigens, effective immune-therapeutics are not presently available and the treatment of chemo-refractory T-ALL is still an unmet clinical need. To develop novel immune-therapy for T-ALL, we generated an afucosylated monoclonal antibody (mAb) (ahuUMG1) and two different bispecific T-cell engagers (BTCEs) against UMG1, a unique CD43-epitope highly and selectively expressed by T-ALL cells from pediatric and adult patients.MethodsUMG1 expression was assessed by immunohistochemistry (IHC) on a wide panel of normal t…

Emergency management in patients with haemophilia A and inhibitors on prophylaxis with emicizumab: AICE practical guidance in collaboration with SIBi…

2020

Emicizumab has been approved in several countries for regular prophylaxis in patients with congenital haemophilia A and FVIII inhibitors because it substantially reduces their bleeding risk and improves quality of life. However, although significantly less frequent, some breakthrough bleeds may still occur while on emicizumab, requiring treatment with bypassing or other haemostatic agents. Thrombotic complications have been reported with the associated use of activated prothrombin complex concentrates. In addition, when surgery/invasive procedures are needed while on emicizumab, their management requires multidisciplinary competences and direct supervision by experts in the use of this agen…

Novel immunotherapies in multiple myeloma – chances and challenges

2021

In this review article, we summarize the latest data on antibody-drug conjugates, bispecific T-cell-engaging antibodies, and chimeric antigen receptor T cells in the treatment of multiple myeloma. We discuss the pivotal questions to be addressed as these new immunotherapies become standard agents in the management of multiple myeloma. We also focus on the selection of patients for these therapies and speculate as to how best to individualize treatment approaches. We see these novel immunotherapies as representing a paradigm shift. However, despite the promising preliminary data, many open issues remain to be evaluated in future trials.

Tumor Regression in Cancer Patients by Very Low Doses of a T Cell–Engaging Antibody

2008

Previous attempts have shown the potential of T cells in immunotherapy of cancer. Here, we report on the clinical activity of a bispecific antibody construct called blinatumomab, which has the potential to engage all cytotoxic T cells in patients for lysis of cancer cells. Doses as low as 0.005 milligrams per square meter per day in non–Hodgkin's lymphoma patients led to an elimination of target cells in blood. Partial and complete tumor regressions were first observed at a dose level of 0.015 milligrams, and all seven patients treated at a dose level of 0.06 milligrams experienced a tumor regression. Blinatumomab also led to clearance of tumor cells from bone marrow and liver. T cell–engag…

Bispecific T-Cell Engager (BiTE) Antibody Construct Blinatumomab for the Treatment of Patients With Relapsed/Refractory Non-Hodgkin Lymphoma : Final …

2016

Purpose Blinatumomab is a CD19/CD3 BiTE (bispecific T-cell engager) antibody construct for the treatment of Philadelphia chromosome–negative acute B-lymphoblastic leukemia. We evaluated blinatumomab in relapsed/refractory B-cell non-Hodgkin lymphoma (NHL). Patients and Methods This 3 + 3 design, phase I dose-escalation study determined adverse events and the maximum tolerated dose (MTD) of continuous intravenous infusion blinatumomab in patients with relapsed/refractory NHL. Blinatumomab was administered over 4 or 8 weeks at seven different dose levels (0.5 to 90 μg/m2/day). End points were incidence of adverse events, pharmacokinetics, pharmacodynamics, and overall response rate. Results B…

Treatment of Malignant Ascites with a Second Cycle of Catumaxomab in Gastric Signet Cell Carcinoma - a Report of 2 Cases

2014

<b><i>Summary</i></b><b><i>Background: </i></b>Malignant ascites is a frequent complication in gastrointestinal malignancy and is unresponsive to systemic therapies. Therapeutic options are limited, and repeated paracentesis is associated with increased loss of fluids and proteins, and impaired quality of life. The bi-specific trifunctional antibody catumaxomab has been approved for the treatment of refractory ascites. It has been proposed that repeated application leads to formation of human anti-mouse antibodies with a decrease in effectiveness and potentially hypersensitivity reactions. <b><i>Case Report: </i></b>Her…

Durability of complete response after blinatumomab therapy for relapsed/refractory diffuse large B-cell lymphoma

2020

Despite advances in standards of care, the prognosis of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) remains poor. In these patients, 50–74% fail to respond to next line therapy,...

Future directions in acquired hemophilia A

2021

Targeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy

2018

The approval of the first two monoclonal antibodies targeting CD38 (daratumumab) and SLAMF7 (elotuzumab) in late 2015 for treating relapsed and refractory multiple myeloma (RRMM) was a critical advance for immunotherapies for multiple myeloma (MM). Importantly, the outcome of patients continues to improve with the incorporation of this new class of agents with current MM therapies. However, both antigens are also expressed on other normal tissues including hematopoietic lineages and immune effector cells, which may limit their long-term clinical use. B cell maturation antigen (BCMA), a transmembrane glycoprotein in the tumor necrosis factor receptor superfamily 17 (TNFRSF17), is expressed a…