Immunotoxins for leukemia

Abstract

Unconjugated monoclonal antibodies that target hematopoietic differentiation antigens have been developed to treat hematologic malignancies. Although some of these have activity against chronic lymphocytic leukemia and hairy cell leukemia, in general, monoclonal antibodies have limited efficacy as single agents in the treatment of leukemia. To increase their potency, the binding domains of monoclonal antibodies can be attached to protein toxins. Such compounds, termed immunotoxins, are delivered to the interior of leukemia cells based on antibody specificity for cell surface target antigens. Recombinant immunotoxins have been shown to be highly cytotoxic to leukemic blasts in vitro, in xenograft model systems, and in early-phase clinical trials in humans. These agents will likely play an increasing role in the treatment of leukemia.

Viscoelastic Properties Measurement of Human Lymphocytes by Atomic Force Microscopy Based on Magnetic Beads Cell Isolation

“…In the past decades, a growing monoclonal antibodies have been developed to treat leukemia and lymphomas, which achieve unprecedented success in clinical practice [51], [52]. However, there are still many patients who develop resistance to the antibody-containing immunotherapy (or relapse after the treatment) and so far the in vivo underlying mechanisms of drug resistance are still unknown [53].…”

Boosting Antitumor Drug Efficacy with Chemically Engineered Multidomain Proteins

“…17, 18, 19, 20 However, the development of effective recombinant chimeras is often laborious;17 bioactivities can be reduced;21 and there are limited opportunities through biosynthesis to further improve pharmacokinetic parameters and therapeutic efficacy such as the attachment of stabilizing polymers or fusion of multiple copies of biomolecules, particularly cyclic peptides 22, 23, 24, 25, 26. Even though synthetic approaches have managed to overcome some of these technological hurdles, the application of chemical strategies alone may be insufficient to prepare multidomain protein conjugates with structural precision and bioactivity 27, 28.…”

Novel Targeted Therapy for Precursor B-Cell Acute Lymphoblastic Leukemia: Anti-CD22 Antibody-MXD3 Antisense Oligonucleotide Conjugate

“…Although monoclonal antibodies (mAbs), as a single agent, have limited therapeutic efficacy, they have improved efficacy when combined with standard induction therapy (13). Furthermore, mAbs have been shown to have a role as cell-targeting agents as in Ab-drug (14)(15)(16) or -immunotoxin (17)(18)(19)(20) conjugates. More recently, there have been promising results with Ab constructs that redirect has improved dramatically through the introduction of intensive combination chemotherapy since the 1960s, the prognosis for certain subtypes remains very poor, with cure rates of approximately 30% (6)(7)(8).…”