Antibody-Drug Conjugates: Ushering in a New Era of Cancer Therapy
Joshua Hurwitz1,2, Lucy Roxana Haggstrom3, Elgene Lim1,2
1St. Vincent's Clinical School, Faculty of Medicine and Health, University of New South Wales, Kensington, NSW 2053, Australia.
Abstract:
Antibody-drug conjugates (ADCs) have provided new therapeutic options and significant promise for patients with cancer, particularly where existing treatments are limited. Substantial effort in ADC development is underway globally, with 13 ADCs currently approved and many more in development. The therapeutic benefits of ADCs leverage the ability to selectively target cancer cells through antibody binding, resultant relative sparing of non-malignant tissues, and the targeted delivery of a cytotoxic payload. Consequently, this drug class has demonstrated activity in multiple malignancies refractory to standard therapeutic options. Despite this, limitations exist, including narrow therapeutic windows, unique toxicity profiles, development of therapeutic resistance, and appropriate biomarker selection. This review will describe the development of ADCs, their mechanisms of action, pivotal trials, and approved indications and identify common themes. Current challenges and opportunities will be discussed for this drug class in cancer therapeutics at a time when significant developments in antibody therapies, immunotherapy, and targeted agents are occurring.
Insights
Antibody-drug conjugates (ADCs) offer targeted cancer therapy by delivering cytotoxic payloads to tumor cells. This review explores their development, benefits, challenges, and future potential in oncology.
Area of Science:
- Oncology
- Pharmacology
- Biotechnology
Background:
- Antibody-drug conjugates (ADCs) represent a significant advancement in cancer therapeutics, offering targeted treatment options.
- The global development of ADCs is substantial, with 13 currently approved and numerous others in clinical trials.
- ADCs leverage selective antibody targeting to deliver cytotoxic payloads, demonstrating efficacy in various refractory malignancies.
Purpose of the Study:
- To review the development and mechanisms of action of antibody-drug conjugates (ADCs).
- To discuss pivotal clinical trials, approved indications, and common themes in ADC therapy.
- To identify current challenges and future opportunities for ADCs in cancer treatment.
Main Methods:
- Literature review of ADCs in cancer therapy.
- Analysis of pivotal clinical trials and approved indications.
- Discussion of mechanisms of action, toxicity profiles, and resistance.
Main Results:
- ADCs demonstrate targeted activity in multiple malignancies, offering alternatives where standard treatments fail.
- Approved ADCs highlight the therapeutic benefits of selective cancer cell targeting and payload delivery.
- Limitations include narrow therapeutic windows, unique toxicities, and resistance development.
Conclusions:
- ADCs provide a promising therapeutic strategy for cancer patients, especially those with limited options.
- Continued research is essential to overcome challenges like toxicity and resistance, and to optimize biomarker selection.
- The future of ADCs is bright, with ongoing developments in antibody therapies, immunotherapy, and targeted agents.
More Related Videos
11:02Genetic Encoding of a Non-Canonical Amino Acid for the Generation of Antibody-Drug Conjugates Through a Fast Bioorthogonal Reaction
Published on: September 14, 2018
15:04Potentiation of Anticancer Antibody Efficacy by Antineoplastic Drugs: Detection of Antibody-drug Synergism Using the Combination Index Equation
Published on: January 19, 2019
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
01:27Tumor Immunotherapy
01:30Cancer Vaccines
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
01:26Antibody Actions
Neutralization
Antibodies can bind to pathogens, preventing them from infecting host cells. This process...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...