Title:Probable Mechanisms Involved in Immunotoxin Mediated Capillary Leak Syndrome (CLS) and Recently Developed Countering Strategies
Volume: 18
Issue: 5
Author(s): B. Darvishi, L. Farahmand, N. Jalili and K. Majidzadeh-A*
Affiliation:
- Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran,Iran
Keywords:
Vascular leak syndrome, immunogenicity, cytokines, immunotoxins, binding side barrier, lymphokineactivated
killer cells.
Abstract: Antibody-toxin fused agents or immunotoxins, are a newly engineered class
of cytotoxic agents consisting of a bacterial or plant toxin moiety hooked up either to a
monoclonal antibody or a specific growth factor. Nevertheless, acquiring a full potency in
clinic is mostly restricted due to the Capillary leak syndrome (CLS), a serious immune
provoked, life-threatening side effect, subsequent to the endothelial damage, resulting in
fluid escape from the bloodstream into tissues including lungs, muscle and brain,
developing organ failure and eventually death. Proposed underlying mechanisms
include direct damage to endothelial cells, acute inflammation, Lymphokine-activated
killer (LAK) cells engagement, alteration in cell-cell/cell-matrix connectivities and
cytoskeletal dysfunction. Very poor biodistribution and heterogeneous extravasation
pattern in tumor site result in accumulation of ITs close to the extravasation site, gradual
toxin release and initiation of nearby endothelial cells lysis, secretion of pro-inflammatory
cytokines, development of acute inflammation and engagement of Lymphokine-activated
killer (LAK) cells. Intrinsic immunogenicity of applied toxin moiety is another important
determinant of CLS incidence. Toxins with more intrinsic immunogenicity possess more
probability for CLS development. Recently, development of new generations of
antibodies and mutated toxins with conserved cytotoxicity has partly tapered risk of CLS
development. Here, we describe probable mechanisms involved in CLS and introduce
some of the recently applied strategies for lessening incidence of CLS as much as
possible.
