Antibody-Drug Conjugates: Can Coupling Cytotoxicity and Specificity Overcome Therapeutic Resistance?

摘要: As their name implies, antibody-drug conjugates (ADCs) comprise a humanized or fully human IgG coupled to cytotoxic small molecule payload. The former component provides the ADC with an antibody’s exquisite selectivity for its target antigen, which is typically cell surface tumor-restricted expression pattern. latter highly potent payload that can efficiently kill targeted cells at low concentrations (sub nM). relatively recent additions armament of anti-cancer drugs, ADCs hold great promise disease management, particularly respect difficult treat, drug-resistant tumors. Here, we provide overview modern approaches cancer treatment, from first-generation systemically delivered chemotherapeutics, through contemporary use molecularly-targeted molecules and biologics, culmination both these approaches—the ADC. Next, detail particular features relate potential overcoming drug resistance, namely, linker component. exceptionally well-suited modifications render payloads poor substrates multidrug transporter-mediated efflux cell. Finally, touch on possibility might also serve as effective means treat tumors are resistant unmodified monoclonal antibody therapies (e.g., rituximab trastuzumab).