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Clinical overview of anti-CD19 BiTE(®) and ex vivo data from anti-CD33 BiTE(®) as examples for retargeting T cells in hematologic malignancies.

Abstract
Blinatumomab, a bispecific antibody construct targeting CD19, is the most advanced member of bispecific T-cell engager (BiTE(®)) molecules. The clinical development program includes B-precursor acute lymphoblastic leukemia (ALL) and B-cell non-Hodgkin lymphoma (NHL). Minimal residual disease (MRD) response in patients with MRD-positive B-precursor ALL has translated into long-term clinical benefits as demonstrated by an estimated relapse-free survival (RFS) of 60% with sustained MRD negativity at a follow-up of 31 months. Remissions induced in pediatric and adult patients with relapsed/refractory B-precursor ALL have allowed for successful allogeneic hematopoietic stem cell transplantation (HSCT) in this setting. Blinatumomab has also induced durable responses in low-grade B-cell NHL. Blinatumomab recently gained approval in the United States by the U.S. Food and Drug Administration for treatment of Philadelphia chromosome-negative B-precursor relapsed/refractory acute lymphoblastic leukemia. AMG 330 is an investigational anti-CD33 BiTE(®) antibody construct. Targeting CD33 ex vivo in primary samples from patients with acute myeloid leukemia (AML) has shown AMG 330-mediated T-cell expansion and T-cell cytotoxicity against AML cells.
AuthorsGerhard Zugmaier, Matthias Klinger, Margit Schmidt, Marion Subklewe
JournalMolecular immunology (Mol Immunol) Vol. 67 Issue 2 Pt A Pg. 58-66 (Oct 2015) ISSN: 1872-9142 [Electronic] England
PMID25883042 (Publication Type: Journal Article, Review)
CopyrightCopyright © 2015 Elsevier Ltd. All rights reserved.
Chemical References
  • Antibodies, Bispecific
  • Antigens, CD19
  • Antineoplastic Agents
  • Sialic Acid Binding Ig-like Lectin 3
  • blinatumomab
  • AMG 330
Topics
  • Antibodies, Bispecific (immunology, therapeutic use)
  • Antigens, CD19 (immunology, metabolism)
  • Antineoplastic Agents (immunology, therapeutic use)
  • Disease-Free Survival
  • Hematologic Neoplasms (immunology, metabolism, therapy)
  • Humans
  • Sialic Acid Binding Ig-like Lectin 3 (immunology, metabolism)
  • T-Lymphocytes (drug effects, immunology, metabolism)
  • Treatment Outcome

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