Antibody‐Drug Conjugates for the Treatment of Cancer

  title={Antibody‐Drug Conjugates for the Treatment of Cancer},
  author={Johan Flygare and Thomas H. Pillow and Paul Adrian Aristoff},
  journal={Chemical Biology \& Drug Design},
With over 20 antibody‐drug conjugates in clinical trials as well as a recently FDA‐approved drug, it is clear that this is becoming an important and viable approach for selectively delivering highly cytotoxic agents to tumor cells while sparing normal tissue. This review discusses the critical aspects for this approach with an emphasis on the properties of the linker between the antibody and the cytotoxic payload that are required for an effective antibody‐drug conjugate. Different linkers are… 
Fate of Antibody-Drug Conjugates in Cancer Cells
A review of mechanisms and their relevance for future development of ADCs as cancer therapeutics highlight the critical processes that both challenge and help foster the design ofADCs.
Antibody-Drug Conjugates : The Forefront of Targeted Chemotherapy for Cancer Treatment
The design of chemical linkers to covalently bind these building blocks is making rapid progress but remains challenging, and recent successes show that the next generation of antibody-drug conjugates has come of age.
Antibody-drug conjugates—a new wave of cancer drugs.
Antibody‐drug conjugates: Promising and efficient tools for targeted cancer therapy
The design of ADCs is reviewed, how ADCs can be exploited to overcome multiple drug resistance (MDR) is focused on, and if appropriate solutions are presented, ADCs will play a more important role in the development of targeted therapeutics against cancer in the next years.
Novel linkers and connections for antibody-drug conjugates to treat cancer and infectious disease.
The efforts at Genentech to develop a new disulfide linker as well as the discovery of a novel quaternary ammonium salt linker connection and the application to ADCs for cancer and infectious disease are focused on.
Antibody-Drug Conjugates and Targeted Treatment Strategies for Hepatocellular Carcinoma: A Drug-Delivery Perspective
This review presents a summary of some of the experimental ADC strategies used in the treatment of hepatocellular carcinoma, from the recent literature.
Challenges and advances in the assessment of the disposition of antibody‐drug conjugates
Factors to consider while assessing the disposition of ADCs, and the unique challenges associated with these therapeutics are discussed.
Preclinical Pharmacokinetic Considerations for the Development of Antibody Drug Conjugates
The pharmacokinetic considerations for an ADC are discussed and tools and strategies that can be used to evaluate molecules at the preclinical stage are discussed.
Antibody–Drug Conjugates: A Comprehensive Review
This review provides an overview of the systemic evaluation of each component of an ADC design, improved understanding of the mechanism of action of ADC, and mechanistic pathways involved in ADC resistance and various strategies to optimize ADC design.
Antibody drug conjugate: the “biological missile” for targeted cancer therapy
The history and general mechanism of action of ADCs are reviewed, and the molecular aspects of key components ofADCs and the mechanisms by which these key factors influence the activities of ADC are discussed.


Investigational antibody-drug conjugates for hematological malignancies
Hematological malignancies are particularly suited to the development of ADC therapeutics as their surface proteins are well characterized, and the consequences of expression of the target in thenormal tissue like the bone marrow results in manageable toxicities since, in many cases, the normal tissue can regenerate.
Investigational antibody drug conjugates for solid tumors
Key challenges the ADC field is facing, including potency and safety, can be addressed effectively by introducing novel research concepts with transformational potential for ADC development.
Designing immunoconjugates for cancer therapy
Conjugation chemistry and recombinant technologies have had a significant impact on the therapeutic prospects of immunoconjugates, particularly in hematopoietic diseases, and continued concerted efforts from different scientific disciplines are needed for greater progress in the more challenging therapy of solid tumors.
Antibody–drug conjugates – a perfect synergy
This review summarises progress with development of this new class of drugs, Antibody–drug conjugates (ADCs), and describes separately the antibody and drug elements of ADCs and then examines the technology and consequences of linkage.
Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies.
Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies (mAbs) with the potency of cytotoxic molecules, thereby taking advantage of the best characteristics of both
Antibody-drug conjugates: basic concepts, examples and future perspectives.
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Arming antibodies for cancer therapy.
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Tumor specific novel taxoid-monoclonal antibody conjugates.
New taxoids bearing methyldisulfanyl(alkanoyl) groups were designed, synthesized, and their activities evaluated, and conjugated to monoclonal antibodies recognizing the epidermal growth factor receptor (EGFR) resulted in complete inhibition of tumor growth in all the treated mice without any noticeable toxicity to the animals.
Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index
The favorable in vivo properties of the near-homogenous composition of this conjugate suggest that the strategy offers a general approach to retaining the antitumor efficacy of antibody-drug conjugates, while minimizing their systemic toxicity.
Antibody-targeted chemotherapy with immunoconjugates of calicheamicin.