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Resistance to Monoclonal Antibody Therapeutics in Lymphoma

  • Matthew J. BarthEmail author
  • Stanton C. Goldman
Chapter
Part of the Resistance to Targeted Anti-Cancer Therapeutics book series (RTACT, volume 21)

Abstract

With the long history of rituximab use in CD20 positive lymphomas and the recent approval of brentuximab vedotin for the treatment of Hodgkin lymphoma and anaplastic large cell lymphoma, monoclonal antibody-based therapies are commonly utilized for the treatment of many lymphomas. Following decades of experience with rituximab, much has been learned about the mechanisms of action and potential mechanisms of resistance to monoclonal antibody therapies, but a thorough understanding of which mechanisms of action are most relevant to rituximab’s efficacy and which resistance mechanisms are most clinically relevant is still elusive. Nonetheless, many approaches have been identified and continue to be investigated both pre-clinically and clinically to attempt to overcome or circumvent resistance to monoclonal antibody therapies in order to enhance treatment responses or improve survival at the time of relapse following monoclonal antibody based therapy.

Keywords

Monoclonal antibody Antibody drug conjugate Non-Hodgkin lymphoma Hodgkin lymphoma Resistance 

Abbreviations

ADCC

Antibody-Dependent Cellular Cytotoxicity

ADPC

Antibody-Dependent Phagocytic Cytotoxicity

AKT

Protein Kinase B

ALCL

Anaplastic Large Cell Lymphoma

ALL

Acute Lymphoblastic Leukemia

B-NHL

B-cell Non-Hodgkin Lymphoma

BiTE

Bispecific T-cell Engaging

CDC

Complement Dependent Cytotoxicity

CLL

Chronic Lymphocytic Leukemia

DLBCL

Diffuse Large B-Cell Lymphoma

EFS

Event-Free Survival

ERK1/2

Extracellular signal Related Kinase 1 and 2

GM-CSF

Granulocyte-Macrophage Colony Stimulating Factor

HACA

Human Anti-Chimera Antibodies

IFN-γ

Interferon Gamma

IL-2

Interleukin 2

IL-4

Interleukin 4

MAPK

Mitogen Activated Protein Kinase

MMAE

Monomethyl Aurostatin E

MS4A1

Membrane Spanning 4-Domain A1

NADPH

Nicotinamide Adenine Dinucleotide Phosphate

NK-κB

Nuclear Factor Kappa B

NK-cell

Natural Killer Cells

PCD

Programmed Cell Death

PLCγ2

Phospholipase C Gamma 2

RIC

Radioimmunoconjugate

ROS

Reactive Oxygen Species

STAT3

Signal Transducer and Activator of Transcription 3

SYK

Spleen Associated Tyrosine Kinase

TNF-α

Tumor Necrosis Factor alpha

Notes

Acknowledgements

S.C.G. is supported by Hyundai Hope on Wheels.

Disclosure of Conflict of Interest

No potential conflicts of interest were disclosed.

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Pediatric Hematology/Oncology, Jacobs School of Medicine and Biomedical SciencesUniversity at BuffaloBuffaloUSA
  2. 2.Department of PediatricsRoswell Park Comprehensive Cancer CenterBuffaloUSA
  3. 3.Division of Pediatric Hematology/OncologyMedical City Children’s HospitalDallasUSA

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