Benefits and challenges of antibody drug conjugates as novel form of chemotherapy

• Published in: Journal of controlled release 2022-01, Vol.341, p.555-565
• Main Authors: Fatima, Syeda Warisul, Khare, Sunil K.
• Format: Article
• Language: English
• Subjects: Antibody conjugated nanoparticles; Antibody drug conjugate; Cancer therapy; Linker; Payload; Targeted drug delivery
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2021.12.013

Antibody drug conjugates (ADCs) are an emerging therapeutic modality for targeted cancer treatment. They represent the unique amalgamation of chemotherapy and immunotherapy. ADCs comprise of monoclonal antibodies linked with drugs (payloads) through a chemical linker designed to deliver the cytotoxic moiety to the cancer cells. The present paper is a review of recent clinical advances of each component of ADCs (antibody/linker/payload) and how the individual component influences the activity of ADCs. The review discusses opportunities for improving ADCs efficiency and ways to have a better antibody-based molecular platform, which could substantially increase chemotherapy outcomes. This review casts an outlook on how ADCs enhancement in terms of their pharmacokinetics, therapeutic indexes and safety profiles can overcome the prevailing challenges like drug resistance in cancer treatment. A novel strategy of augmenting antibodies with nanoparticles anticipates a huge success in terms of targeted delivery of drugs in several diseases. Antibody conjugated nanoparticles (ACNPs) are a very promising strategy for the cutting-edge development of chemo/immunotherapies for efficient delivery of payloads at the targeted cancer cells. The avenues of a high drug to antibody ratio (DAR) owing to the selection of broad chemotherapy payloads, regulating drug release eliciting higher avidity of ACNPs over ADCs will be the modern immunotherapeutics. ACNPs carry immense potential to mark a paradigm shift in cancer chemotherapy that may be a substitute for ADCs. [Display omitted] •Antibody drug conjugates are mAbs linked with cytotoxic payloads.•ADCs-ACNPs are the recent advances in immuno-chemo-oncology.•ADCs are therapeutic modalities embedded with high mAb specificity and efficacy.•Progress to the perfection of how ADCs deliver payloads onto the tumor is presented.•The emerging therapeutic options for cancer treatment are discussed.