Passive and catalytic antibodies and drug delivery

Abstract

Antibodies are one of the most promising components of the biotechnology repertoire for the purpose of drug delivery. On the one hand, they are proven agents for cell-selective delivery of highly toxic agents in a small but expanding number of cases. This technology calls for the covalent attachment of the cytotoxin to a tumor-specific antibody by a linkage that is reversible under appropriate conditions (antibody conjugate therapy, ACT-"passive delivery"). On the other hand, the linker cleavage can be accomplished by a protein catalyst attached to the tumor-specific antibody ("catalytic delivery"). Where the catalyst is an enzyme, this approach is known as antibody-directed enzyme prodrug therapy (ADEPT). Where the transformation is brought about by a catalytic antibody, it has been termed antibody-directed abzyme prodrug therapy (ADAPT). These approaches will be illustrated with emphasis on how their demand for new biotechnology is being realized by structure-based protein engineering.

Painting the Target Around the Arrow: Two-Step Prodrug Therapies from a Carbohydrate Chemists Perspective

“…Both passive and catalytic antibodies continue to be widely explored as tools in drug delivery [25]. The antibody-based twostep prodrug therapies generally release the prodrug in extracellular space, while gene-based approaches can be used to activate a prodrug intracellularly if the medicinal agent has sufficient membrane permeability (Fig.…”

Quinone Methide Signal Amplification: Covalent Reporter Labeling of Cancer Epitopes using Alkaline Phosphatase Substrates

“…Enzyme substrates capable of forming QMs were initially investigated as potential mechanism-based inhibitors of hydrolase-type enzymes. − Later, they were employed as self-immobilizing probes for enzyme activities, including phosphatases, − sulfatases, , glycosidases, ,− lipases, and β-lactamases . While the majority of these examples involved the detection of enzyme activity in solution or on Western blot, a recent publication from Withers reported fluorescent histological staining on plant tissue utilizing coumarin glycosides modified to generate QMs upon reaction with their cognate endogenous glycosidase .…”