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

Mol Immunol. 2015 Oct;67(2 Pt A):58-66. doi: 10.1016/j.molimm.2015.02.033. Epub 2015 Apr 13.

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.

Keywords: ALL; AMG 330; AML; BiTE; Blinatumomab; Immunotherapy; NHL.

Publication types

  • Review

MeSH terms

  • Antibodies, Bispecific / immunology
  • Antibodies, Bispecific / therapeutic use*
  • Antigens, CD19 / immunology*
  • Antigens, CD19 / metabolism
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / therapeutic use
  • Disease-Free Survival
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / metabolism
  • Hematologic Neoplasms / therapy*
  • Humans
  • Sialic Acid Binding Ig-like Lectin 3 / immunology*
  • Sialic Acid Binding Ig-like Lectin 3 / metabolism
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Treatment Outcome

Substances

  • Antibodies, Bispecific
  • Antigens, CD19
  • Antineoplastic Agents
  • Sialic Acid Binding Ig-like Lectin 3
  • blinatumomab
  • AMG 330