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Resistance to Antibody-Drug Conjugate

  • Jessica HochbergEmail author
  • Sarah Alexander
Chapter
Part of the Resistance to Targeted Anti-Cancer Therapeutics book series (RTACT, volume 21)

Abstract

Immune therapies have shown significant efficacy in the treatment of pediatric lymphomas. Monoclonal antibodies, whether naked or conjugated have emerged as an attractive option for targeted therapy while minimizing toxicities. Monoclonal antibodies conjugated to small molecule drugs were developed as a way to combine highly potent agents with tumor specificity. Current challenges include careful selection of tumor targets, the management of potential toxicities, identification of ideal patient selection and therapy regimens, and a better understanding of antibody-drug conjugates (ADC) mechanisms of action and resistance. The right combination is critical for a successful ADC. Mechanisms of resistance to ADCs can be inherited to the ADC or acquired by the host environment and can developed against each of the individual components of the ADC. Given the rational design of ADCs, there is the ability to modify each of the components to develop improved agents that can overcome resistance.

Keywords

Pediatrics Lymphoma Antibody Conjugates Resistance Immunotherapy 

Abbreviations

ABVD

Doxorubicin, Bleomycin, Vinblastine, Dacarbazine

ADC

Antibody-Drug Conjugate

ADCC

Antibody Dependent Cellular Cytotoxicity

Ag-Ab

Antigen-Antibody

AKT

Activated Tyrosine Kinase

ALCL

Anaplastic Large Cell Lymphoma

ALL

Acute Lymphoblastic Leukemia

AML

Acute Myeloid Leukemia

AVD

Doxorubicin, Vinblastine, Dacarbazine

Bv

Brentuximab Vedotin

CI

Confidence Interval

COG

Children’s Oncology Group

CR

Complete Response

DLBCL

Diffuse Large B-Cell Lymphoma

FDA

Food and Drug Administration

GO

Gemtuzumab Ozogamicin

HL

Hodgkin Lymphoma

HR

Hazard Ratio

IO

Inotuzumab Ozogamicin

mAB

Monoclonal Antibody

MF

Mycosis Fungoides

MMAE

Monomethylauristatin E

NHL

Non-Hodgkin Lymphoma

OR

Objective Response

pcALCL

Primary cutaneous Anaplastic Large Cell Lymphoma

PFS

Progression-Free Survival

RR

Response Rate

Notes

Disclosure of Conflict of Interest

No potential conflicts of interest were disclosed.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Hematology, Oncology & Stem Cell Transplant, Maria Fareri Children’s Hospital at Westchester Medical CenterNew York Medical CollegeValhallaUSA
  2. 2.Division of Haematology/OncologyThe Hospital for Sick ChildrenTorontoCanada

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