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Resistance to Bispecific T-Cell Engagers and Bispecific Antibodies

  • Stacy L. CooperEmail author
  • Patrick A. Brown
Chapter
Part of the Resistance to Targeted Anti-Cancer Therapeutics book series (RTACT, volume 21)

Abstract

Bispecific antibodies are an emerging novel therapeutic construct used to treat a variety of cancers. These drugs utilize a small fusion protein to link two single-chain antibodies, allowing for simultaneous binding of two different epitopes. Bispecific T-cell engagers (BiTE) are a subset of bispecific antibodies that bind the target antigen on the cancer cell while simultaneously binding a patient’s endogenous T-cell. By bringing these two cells in close proximity, the patient’s own immune system can be redirected to attack the cancer cell. Several mechanisms of resistance to these drugs exist, including extramedullary escape, loss of the target antigen, and inadequate endogenous immune response.

Keywords

Bispecific antibodies BiTE Blinatumomab Non-Hodgkin lymphoma Acute lymphoblastic leukemia 

Abbreviations

B-ALL

B Acute Lymphoblastic Leukemia

BiTE

Bi-Specific Antigen Receptor T-Cells

CAR-T

Chimeric Antigen Receptor T-cells

CNS

Central Nervous System

CR

Complete Response Rate

CRS

Cytokine Release Syndrome

DLBCL

Diffuse Large B-Cell Lymphoma

EM

Extramedullary

EFS

Event-Free Survival

FDA

Food and Drug Administration

HL

Hodgkin Lymphoma

MCH

Major Histocompatibility Complex

MLL

Mixed Lineage Leukemia

NHL

Non-Hodgkin Lymphoma

NK

Natural Killer

ORR

Overall Response Rate

OS

Overall Survival

PD-L1

Programmed Death Ligand 1

PD-1

Programmed Death Protein 1

R/R

Relapsed/Refractory

scFv

Single-chain Fragment Variable

TCR

T-Cell Receptor

Treg

Regulatory T-Cell

Notes

Disclosure of Conflict of Interest

No potential conflicts of interest were disclosed by SC. P.B. has received medical writing support from Amgen for an unrelated manuscript.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Pediatric Oncology, Department of OncologyJohns Hopkins University School of MedicineBaltimoreUSA

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