Designing immunoconjugates for cancer therapy

Abstract

Introduction: Antibody–drug conjugates (ADCs), as well as antibody conjugates of protein toxins (immunotoxins) and cytokines (immunocytokines), are showing clinical efficacy, with manageable toxicities, in cancer treatment.

Areas covered: The utility of an ADC is governed by the antibody and the target, as well as by the drug–linker component of the conjugate. The conjugation site, conjugating group, drug/antibody ratios and site-specific conjugation for product homogeneity are all aspects to consider in optimizing the ADC and enhancing its therapeutic window. Immunotoxin and immunocytokine construction by recombinant methods can be modulated to improve efficacy and reduce toxicity. The Dock-and-Lock (DNL) platform technology provides a flexible approach to assemble mono- or bispecific constructs carrying multiple toxin or cytokine molecules for targeted therapy.

Expert opinion: Conjugation chemistry and recombinant technologies have had a significant impact on the therapeutic prospects of immunoconjugates, particularly in hematopoietic diseases. Continued concerted efforts from different scientific disciplines are needed, together with newer treatment paradigms, for greater progress in the more challenging therapy of solid tumors.

Keywords::

• antibody–drug conjugate
• cancer
• cross-linker
• Dock-and-Lock
• immunocytokine
• immunotoxin
• therapeutic index

Acknowledgement

We thank RM Sharkey of Immunomedics, Inc., for providing Figure 1.

Notes

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