Antibody-drug conjugates: a mini-review. The synopsis of two approved medicines

Abstract

Targeted drug delivery is a method of delivering bioactive compounds to a patient in a manner that increases the therapeutic index. The main goal of a targeted drug delivery system is to prolong, localize, target and have a protected drug interaction with the diseased tissue. Antibody-drug conjugates (ADC) represent an innovative therapeutic application that combines the unique properties of monoclonal antibodies with the potent cell killing activity of cytotoxic bioactive compounds. ADCs are complex molecules composed of an antibody linked, via a stable, chemical, linker with labile bonds, to a biological active cytotoxic (anticancer) payload or drug. The key components of ADC include a monoclonal antibody, a stable linker and a cytotoxic agent to target a variety of cancers. The present mini-review deals with the examination of clinical use and pharmacological properties, as well as the safety of antibody-drug conjugates that are marketed. Ado-trastuzumab emtasine and brenduximab vedotin were examined regarding their mechanism of action, pharmacology, clinical use and safety. These ADCs selectively deliver cargoes to tumor cells and provide clinical benefit by minimizing systemic toxicity.

In Vivo Translation of Peptide-Targeted Drug Delivery Systems Discovered by Phage Display

“…Drug delivery strategies are designed to address challenges associated with drug bioavailability, stability, solubility, and toxicity, as well as physiological barriers to cellular entry. − Compounds with narrow therapeutic indices are particularly well-suited for administration by targeted drug delivery systems to avoid off-target effects in healthy tissues . Early drug targeting systems exploited antibody-functionalized liposomes to enhance cell uptake and reduce systemic off-target accumulation. , Recent efforts focus on peptides as targeting ligands, which can exhibit homology to antibodies and other native proteins, but are more economical and reproducible and are less likely to induce an immune response. , …”

Guanylate cyclase C as a target for prevention, detection, and therapy in colorectal cancer

“…The next generation of antibody therapies, antibody-drug conjugates (ADCs) enable targeted delivery of cytotoxic agents to specific tissues [89, 90]. ADCs are engineered by linking a cytotoxin to a monoclonal antibody, facilitating targeting to cells expressing cancer antigens, endocytic uptake, and intracellular delivery of the toxic payload.…”

“…Conceptually, the targeted nature of ADCs reduces systemic exposure, and endocytic uptake reduces drug resistance by P-glycoprotein efflux pump, two of the pitfalls of existing chemotherapeutics [89]. However, as a relatively new drug class, ADCs historically have proven difficult to optimize, and have been associated with significant side effects due to non-specific targeting [90]. For this reason, only two have achieved FDA approval, adotrastuzumab emtasine and brentuximab vedotin, although several others have entered clinical trials.…”

Enhancement of in vitro antitumour activity of epirubicin in HER2+ breast cancer cells using immunoliposome formulation

“…On the other hand, targeted drug delivery systems can improve treatment efficacy and therapeutic index. One of the most interesting agents for targeted therapy is antibodies or antibody fragments as they are cytotoxic and have the cell killing potential in addition to addressing therapeutic agent to tumour site [ 6 ]. Overexpression of human epidermal growth factor receptor 2 (HER2) in 25%–30% of BCs occurs and can be a target receptor for the antibody trastuzumab (Herceptin™) [ 7 ].…”