Antibody-mediated delivery of therapeutics for cancer therapy

ABSTRACT

Introduction: Antibody-conjugated therapies (ACTs) combine the specificity of monoclonal antibodies to target cancer cells directly with highly potent payloads, often resulting in superior efficacy and/or reduced toxicity. This represents a new approach to the treatment of cancer. There have been highly promising clinical trial results using this approach with improvements in linker and payload technology. The breadth of current trials examining ACTs in haematological malignancies and solid tumours indicate the potential for clinical impact.

Areas covered: This review will provide an overview of ACTs currently in clinical development as well as the principles of antibody delivery and types of payloads used, including cytotoxic drugs, radiolabelled isotopes, nanoparticle-based siRNA particles and immunotoxins.

Expert opinion: The focus of much of the clinical activity in ACTs has, understandably, been on their use as a monotherapy or in combination with standard of care drugs. This will continue, as will the search for better targets, linkers and payloads. Increasingly, as these drugs enter routine clinical care, important questions will arise regarding how to optimise ACT treatment approaches, including investigation of resistance mechanisms, biomarker and patient selection strategies, understanding of the unique toxicities of these drugs, and combinatorial approaches with standard therapies as well as emerging therapeutic agents like immunotherapy.

KEYWORDS:

• Antibody-conjugated therapies
• immunotoxins
• radioimmunotherapy
• siRNA

Declaration of Interest

H Gan has research funding from AbbVie Pharmaceuticals, is on an Advisory board for AbbVie and Merck Serono, and has received travel support/honoraria/speaker bureau for Merck Serono, AbbVie, Pfizer, Bayer, Novartis and Merck. A Scott has research funding support from AbbVie Pharmaceutics and Daiichi-Sankyo Co, is an inventor of mAb806, and has a consultancy and stock ownership of Life Science Pharmaceuticals. The authors have funding support from NHMRC [Fellowship 1,084,178 and Grants 1087850, 1030469, 1,075,898 (AMS)], Cancer Australia, Ludwig Cancer Research, John T Reid Trusts, Cure Brain Cancer Foundation, and the Victoria Cancer Agency. Funding from the Operational Infrastructure Support Program provided by the Victorian Government, Australia is also acknowledged. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.