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Delivering More Payload (High DAR ADCs)

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Innovations for Next-Generation Antibody-Drug Conjugates

Part of the book series: Cancer Drug Discovery and Development ((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.

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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

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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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  1. Mersana Therapeutics, Inc., Cambridge, MA, USA

    Natalya Bodyak

  2. Valley Cross Consulting, Inc., North Grafton, MA, USA

    Alexander V. Yurkovetskiy

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  1. Natalya Bodyak
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  2. Alexander V. Yurkovetskiy
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Correspondence to Natalya Bodyak .

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  1. Mersana Therapeutics, Inc., Cambridge, Massachusetts, USA

    Marc Damelin

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Bodyak, N., Yurkovetskiy, A.V. (2018). Delivering More Payload (High DAR ADCs). In: Damelin, M. (eds) Innovations for Next-Generation Antibody-Drug Conjugates. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-78154-9_9

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  • DOI: https://doi.org/10.1007/978-3-319-78154-9_9

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