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Delivering More Payload (High DAR ADCs)

  • Natalya Bodyak
  • Alexander V. Yurkovetskiy
Chapter
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

Antibody drug conjugates (ADCs) for oncology applications are chemotherapeutic agents designed to selectively deliver cytotoxic drug payloads to neoplastic tissue. This book chapter reviews the latest approaches for high drug loaded ADCs. The primary focus of this review is related to ADC drug payload and antibody-drug bioconjugation linker selection strategies resulting in biotherapeutics with improved physicochemical properties, efficacy, and pharmacokinetics. A separate section of this chapter gives a brief overview of antibody targeted nanotherapeutics, a growing and diverse class of anti-cancer agents specifically designed for delivery of significant amounts of drug payload. New strategies to design the highly potent antibody targeted agents discussed in this chapter provide the opportunity to expand the list of drug payloads suitable for ADC applications and introduce agents with new mechanisms of action, which in turn may potentially lead to improvement in therapeutic index of the ADCs for the treatment of cancer.

Keywords

Antibody drug conjugates High DAR ADCs High drug loaded ADCs Nanotherapeutics 

Abbreviations

ADC

Antibody drug conjugate

ADCM

Antibody/drug-conjugated micelle

AM

Aminomethylene

DAR

Drug antibody ratio

EPR

Enhanced permeability and retention

F-HPA

F-hydroxypropylamide

GGFG

Glycine-glycine-phenylalanine-glycine

HPMA

N-(2-hydroxypropyl) methacrylamide

IFN

Interferon

IL

Immunoliposome

MAP-CPT

Mucic acid polymer conjugate of camptothecin

mDPR

Maleimidodiaminopropionic acid

MDR

Multidrug resistance

MMAD

Monomethyl auristatin D

MMAE

Monomethyl auristatin E

MMAF

Monomethyl auristatin F

OC

Ovarian cancer

PBD

pyrrolobenzodiazepine

P-gp

P-glycoprotein

PHF

Poly-1-hydroxymethylethylene hydroxymethylformal

PK

Pharmacokinetics

RES

Reticular endothelial system

SCID

Severe combined immunodeficiency disease

TCEP

Tris-carboxyethylphosphine

TI

Therapeutic index

TNBC

Triple-negative breast cancer

TOPO I

Topoisomerase I

val-cit-PABC

Valine-citrulline-p-aminobenzylcarbamate

Notes

Acknowledgements

The authors thank Radha Iyengar for thoughtful and insightful comments on the manuscript. The authors also thank Theresa E. Singleton, PhD of Singleton Science, LLC for editorial support, which was funded by Mersana Therapeutics in accordance with Good Publication Practice (GPP3) guidelines.

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Mersana Therapeutics, Inc.CambridgeUSA
  2. 2.Valley Cross Consulting, Inc.North GraftonUSA

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