Escape from ALL-CARTaz: Leukemia Immunoediting in the Age of Chimeric Antigen Receptors

Sisi Zheng, Mukta Asnani, Andrei Thomas-Tikhonenko

Research output: Contribution to journalReview articlepeer-review

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has been transformative for the treatment of B-cell malignancies, with CD19- and CD22-directed CARs being prime examples. However, immunoediting and ensuing antigen loss remain the major obstacles to curative therapy in up to 25% of patients. For example, to achieve the CD19-negative phenotype, malignant cells can pick from a broad array of mechanisms, including focal loss-of-function mutations, dysregulated trafficking to the cell surface, alternative splicing, and lineage switching. In other cases, where resistance is mediated by insufficient antigen density, trogocytosis has been proposed as a possible underlying mechanism. To overcome these barriers, compensatory strategies will be needed, which could include using combinatorial CARs, harnessing epitope spreading, and targeting tumor neoantigens.

Original languageEnglish (US)
Pages (from-to)217-222
Number of pages6
JournalCancer Journal
Volume25
Issue number3
DOIs
StatePublished - May 1 2019
Externally publishedYes

Keywords

  • Adoptive T-cell therapy
  • alternative splicing
  • antigen escape
  • chimeric antigen receptors
  • epitope loss
  • immunoediting
  • immunotherapy
  • leukemia
  • lymphoma
  • therapeutic resistance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Escape from ALL-CARTaz: Leukemia Immunoediting in the Age of Chimeric Antigen Receptors'. Together they form a unique fingerprint.

Cite this