Investigational antibody-drug conjugates for hematological malignancies

Abstract

Importance of the field: Antibody-drug conjugates (ADCs) consist of potent cytotoxic drugs linked to antibodies via chemical linkers. ADCs facilitate the specific targeting of drugs to neoplastic cells. This technology is showing efficacy with manageable toxicity for the treatment of hematological malignancies.

Areas covered in this review: ADCs for the treatment of hematological malignancies are in pre-clinical and early clinical trials. This review describes these ADCs in detail and explores the challenges of optimizing the use of this technology.

What the reader will gain: The reader should understand that, although ADCs are conceptually simple, the application of this idea to practice has not been straightforward, and the challenges of developing ADCs include identifying targets with appropriate expression profiles and biology, developing successful linker chemistries, and the selection of a potent cytotoxic drug.

Take home message: 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 the normal tissue like the bone marrow results in manageable toxicities since, in many cases, the normal tissue can regenerate. While this technology is complex, the ADCs for hematological malignancies currently in clinical use show great promise.

Keywords::

• ADCs
• antibody-drug conjugates
• auristatin
• calicheamicin
• duocarmycin
• Hodgkin's lymphoma
• maytansine
• multiple myeloma
• NHL
• non-Hodgkin's lymphoma
• ozogamicin

Notes

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