TITLE:
The ABC of ADCs (Antibody-Drug Conjugates): A Comprehensive Review of Technical, Regulatory, and Clinical Challenges
AUTHORS:
Kishore Kumar Hotha
KEYWORDS:
Antibody-Drug Conjugates, Cancer Therapy, Payload, Linker, Conjugation Chemistry, Antibody, Analytical Development, Manufacturing of ADCs
JOURNAL NAME:
Advances in Chemical Engineering and Science,
Vol.13 No.4,
October
27,
2023
ABSTRACT: Over the past several decades, there has been a
significant surge in the development of
Antibody-Drug Conjugates (ADCs). Designing an ideal ADC presents a
multifaceted challenge, requiring the precise orchestration of various elements
such as antigens, antibodies, linkers, and payloads. While ADCs aim to target
tumor cells specifically, several antigens can also be found in regular
tissues, potentially compromising the specificity of ADCs in therapeutic
applications. The complexity extends to antibody selection, necessitating
effective targeting of the desired antigen and ensuring compatibility with
linkers for effective payload delivery. Additionally, the linker and payload
combination are critical for the ADC’s therapeutic efficiency, balancing
stability in circulation and timely payload release upon target binding. ADC
doses must be safe for normal tissues while ensuring the released payloads are
effective. The success of ADCs is attributed to their unmatched efficacy
compared to traditional chemotherapy agents. The current research article aims
to provide a technical review of Antibody-Drug Conjugates (ADCs) for cancer
therapies. A brief discussion on the basics of ADCs, regulatory approach,
overview, and technical complexities for quantification is presented. This
review also summarizes recently approved ADCs and introduces the concepts of
antibodies, linkers, and payloads. The article also outlines cancer-specific
ADCs currently in late-stage clinical trials for cancer treatment.