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Resistance to Bispecific T-Cell Engagers and Bispecific Antibodies

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Resistance to Targeted Therapies in Lymphomas

Part of the book series: Resistance to Targeted Anti-Cancer Therapeutics ((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.

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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

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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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Authors and Affiliations

  1. Division of Pediatric Oncology, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Stacy L. Cooper & Patrick A. Brown

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  1. Stacy L. Cooper
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  2. Patrick A. Brown
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Correspondence to Stacy L. Cooper .

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Editors and Affiliations

  1. Division of Hematology/Oncology, Department of Pediatrics, University of Alabama at Birmingham Children’s Hospital of Alabama, Birmingham, AL, USA

    Ana C. Xavier

  2. Departments of Pediatrics, Medicine, Pathology, Microbiology and Immunology, Cell Biology and Anatomy, New York Medical College, Valhalla, NY, USA

    Mitchell S. Cairo

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Cooper, S.L., Brown, P.A. (2019). Resistance to Bispecific T-Cell Engagers and Bispecific Antibodies. In: Xavier, A., Cairo, M. (eds) Resistance to Targeted Therapies in Lymphomas . Resistance to Targeted Anti-Cancer Therapeutics, vol 21. Springer, Cham. https://doi.org/10.1007/978-3-030-24424-8_8

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