Related Experiment Video

Updated: Feb 4, 2026

Murine Model of Leukemia Relapse to Induction Chemotherapy for Acute Lymphoblastic Leukemia
08:31

Murine Model of Leukemia Relapse to Induction Chemotherapy for Acute Lymphoblastic Leukemia

Published on: October 17, 2025

697

Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia

Elena J Orlando1, Xia Han2, Catherine Tribouley2

  • 1Novartis Institutes for BioMedical Research, Cambridge, MA, USA. elena.orlando@novartis.com.

Nature Medicine
|October 3, 2018
PubMed

Insights

Genetic mutations in CD19 cause resistance to CAR therapy by eliminating the surface antigen. This irreversible loss necessitates alternative chimeric antigen receptor (CAR) strategies or combination therapies for effective treatment.

Area of Science:

  • Immunology
  • Genetics
  • Oncology

Background:

  • Chimeric antigen receptor (CAR) therapy shows promise for hematologic malignancies.
  • Relapse due to antigen loss remains a significant challenge in CAR therapy.

Purpose of the Study:

  • To investigate the mechanisms of CD19 loss in patients relapsing after CAR therapy.
  • To identify genetic alterations responsible for CD19 antigen escape.

Main Methods:

  • Genetic sequencing of tumor cells from patients with CD19-negative relapse.
  • Analysis of mutations affecting the CD19 gene and protein structure.

Main Results:

  • Identified genetic mutations and loss of heterozygosity in the CD19 gene in relapsed tumor cells.
  • Mutations predicted to result in a truncated, nonfunctional CD19 protein lacking a surface transmembrane domain.
  • Confirmed widespread presence of these mutations in resistant tumor cell populations.

Conclusions:

  • Irreversible loss of the CD19 target antigen is a key mechanism of relapse.
  • Alternative CAR targets or combination CAR approaches are needed to overcome CD19 loss and improve therapeutic outcomes.

More Related Videos

In Ovo Xenografting of Patient-Derived Acute Lymphoblastic Leukemia (ALL) Cells (PDX-ALL)06:48

In Ovo Xenografting of Patient-Derived Acute Lymphoblastic Leukemia (ALL) Cells (PDX-ALL)

Published on: August 1, 2025

533
Isolation of the Side Population in Myc-induced T-cell Acute Lymphoblastic Leukemia in Zebrafish09:06

Isolation of the Side Population in Myc-induced T-cell Acute Lymphoblastic Leukemia in Zebrafish

Published on: May 4, 2017

7.0K

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
8.9K
Line Loss01:10

Line Loss

The different configurations of source-load connections include wye (star) and delta connections. The relationship between line and phase voltages and currents varies depending on the configuration. When the source is supplying power, it is transmitted through the wires to the load, and during this transmission, some power is absorbed by the wires, leading to line loss.
Line loss impacts power delivery efficiency in a balanced three-phase circuit. The symmetry in such a circuit simplifies the...
545
What is Genetic Engineering?00:49

What is Genetic Engineering?

Overview
80.2K
Reducing Line Loss01:18

Reducing Line Loss

In a three-phase circuit, line loss is an indicator of energy dissipated as heat due to the resistance of transmission lines. To address this, incorporating transformers into the system—a step-up transformer at the source and a step-down transformer at the load—is a strategic solution. Two three-phase transformers are introduced to improve this.
With a step-up transformer at the source, the voltage is increased, thereby reducing the current in the transmission lines since power loss in...
390
Genetics of Speciation02:16

Genetics of Speciation

Speciation is the evolutionary process resulting in the formation of new, distinct species—groups of reproductively isolated populations.
21.5K
Types of Genetic Transfer Between Organisms02:18

Types of Genetic Transfer Between Organisms

Genetic transfer occurs when genetic information is passed from one organism to another. It occurs via two mechanisms: vertical gene transfer and horizontal gene transfer. Vertical gene transfer occurs when genetic information is transferred from one generation to the next, which happens much more frequently than horizontal gene transfer. Both sexual and asexual reproduction are forms of vertical gene transfer, where one or more organisms pass some or all of their genome onto their progeny.
30.8K