Antibody-drug conjugates for targeted cancer therapy: Recent advances in potential payloads
Meiyang Xi1, Jingjing Zhu2, Fengxia Zhang2
1Zhejiang Engineering Research Center of Fat-soluble Vitamin, Shaoxing University, Shaoxing, 312000, China; College of Chemistry and Chemical Engineering, Shaoxing University, Shaoxing, 312000, China.
Abstract:
Antibody-drug conjugates (ADCs) represent a promising cancer therapy modality which specifically delivers highly toxic payloads to cancer cells through antigen-specific monoclonal antibodies (mAbs). To date, 15 ADCs have been approved and more than 100 ADC candidates have advanced to clinical trials for the treatment of various cancers. Among these ADCs, microtubule-targeting and DNA-damaging agents are at the forefront of payload development. However, several challenges including toxicity and drug resistance limit the potential of this modality. To tackle these issues, multiple innovative payloads such as immunomodulators and proteolysis targeting chimeras (PROTACs) are incorporated into ADCs to enable multimodal cancer therapy. In this review, we describe the mechanism of ADCs, highlight the importance of ADC payloads and summarize recent progresses of conventional and unconventional ADC payloads, trying to provide an insight into payload diversification as a key step in future ADC development.
Insights
Antibody-drug conjugates (ADCs) offer targeted cancer therapy by delivering potent payloads. Innovations in payload design, including immunomodulators and PROTACs, aim to overcome challenges like toxicity and drug resistance for improved cancer treatment.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Antibody-drug conjugates (ADCs) are an emerging cancer therapy, utilizing monoclonal antibodies (mAbs) to deliver cytotoxic payloads specifically to cancer cells.
- Fifteen ADCs are approved, with over 100 in clinical trials, highlighting their significance in treating diverse cancers.
- Current ADC payloads primarily include microtubule-targeting and DNA-damaging agents, but face limitations due to toxicity and drug resistance.
Purpose of the Study:
- To review the mechanism of action for antibody-drug conjugates (ADCs).
- To emphasize the critical role of payloads in ADC efficacy.
- To summarize advancements in both conventional and novel ADC payloads, exploring strategies to overcome therapeutic challenges.
Main Methods:
- Literature review of antibody-drug conjugate mechanisms and payload development.
- Analysis of current ADC approvals and clinical trial progression.
- Synthesis of information on conventional and innovative payload types, including immunomodulators and proteolysis targeting chimeras (PROTACs).
Main Results:
- ADCs demonstrate a targeted approach to cancer therapy, delivering potent toxins via mAbs.
- Payload diversification is crucial for enhancing ADC efficacy and addressing resistance mechanisms.
- Innovative payloads like immunomodulators and PROTACs are being integrated to enable multimodal cancer treatment strategies.
Conclusions:
- Payload selection and diversification are key determinants of ADC success.
- Overcoming ADC limitations requires exploring novel payloads beyond traditional cytotoxic agents.
- Future ADC development hinges on innovative payload strategies to broaden therapeutic applications and improve patient outcomes.
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