Antibody-drug conjugates: Recent advances in payloads

Area of Science:

• Oncology
• Pharmacology
• Biotechnology

Background:

• Antibody-drug conjugates (ADCs) combine targeted monoclonal antibodies with potent cytotoxic payloads, demonstrating significant clinical therapeutic value.
• ADC payloads are critical for drug efficacy, requiring high toxicity, low immunogenicity, stability, and functional modifiability.
• Traditional payloads like tubulin inhibitors face limitations including inadequate efficacy and acquired drug resistance.

Purpose of the Study:

• To summarize recent research advances in traditional and novel Antibody-drug conjugate payloads.
• To focus on structure-activity relationships, co-crystal structures, and design strategies for ADC payloads.
• To discuss future research directions for developing next-generation ADC payloads.

Main Methods:

• Review of current literature on Antibody-drug conjugate payload research.
• Analysis of structure-activity relationships and co-crystal structures of payloads.
• Synthesis of design strategies for novel ADC payloads.

Main Results:

• Identified key characteristics of ideal ADC payloads: high efficacy, low toxicity, stability, and ability to overcome resistance.
• Highlighted the prevalence and limitations of tubulin inhibitors as common ADC payloads.
• Emphasized the ongoing development of novel payloads with diverse targets and reduced side effects.

Conclusions:

• Novel Antibody-drug conjugate payloads are crucial for advancing cancer therapeutics.
• Future research should focus on payloads with enhanced efficacy, safety profiles, and resistance-overcoming capabilities.
• This review provides references for developing superior ADC payloads to address clinical challenges.