Chemotherapeutic Drug-Antibody Conjugates (ChemoBodies): Recent Advances and Future Directions

Area of Science:

• Biopharmaceutical Development
• Oncology Therapeutics
• Molecular Targeting

Background:

• Antibody-drug conjugates (ADCs) represent a rapidly growing class of biopharmaceuticals with significant therapeutic potential.
• ADCs are utilized for treating both solid and hematological tumors, with numerous products approved and in clinical trials.

Purpose of the Study:

• To comprehensively review and map the components of ADCs, including antibodies, engineered fragments, payloads, linkers, and conjugation chemistry.
• To summarize technologies used in the development of US-FDA-approved and investigational ADC molecules.

Main Methods:

• Analysis of components from approved ADCs.
• Review of antibody engineering, conjugation chemistry, and payload technologies.
• Summarization of technologies for US-FDA-approved and clinical trial ADCs.

Main Results:

• Approved ADCs primarily target hematological tumors (e.g., CD33, BCMA) and solid tumors (e.g., HER2, TROP2).
• Common conjugation methods include succinimide and maleimide chemistry, linking antibodies to DNA-damaging agents, microtubule inhibitors, or topoisomerase inhibitors.
• Advancements in antibody engineering, conjugation, and payloads aim to address current ADC challenges.

Conclusions:

• ADCs are a promising therapeutic class for various cancers.
• Understanding the interplay of antibodies, linkers, payloads, and conjugation chemistry is crucial for ADC development.
• Ongoing technological advancements are expanding the potential of ADCs in cancer treatment.