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August 16, 2026Blood Cancer Discovery

CAR T Cells Targeting an Intracellular Leukemia Antigen Promiscuously Presented by Diverse HLA-II Alleles

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Authors

EZEvey Y. F. ZhengCWChung-Hsi WangTOToshiki Ochi

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Overview

Preclinical study demonstrates that WT1-targeted CAR T cells eliminate leukemia across diverse HLA-II alleles, indicating broad potential applicability for genetically diverse populations.

Key Points

  • To develop and evaluate CAR T cells capable of targeting the intracellular WT1 oncoprotein cross-presented across diverse HLA class II alleles.
  • Generated WT1-specific CAR T cells derived from an antibody raised against the WT1 330-348 peptide.
  • Assessed CAR T-cell recognition of the WT1 peptide presented across 20 distinct HLA class II alleles.
  • Evaluated target-specific antileukemic activity and cytotoxicity in vitro and in vivo.
  • WT1-CAR T cells recognized the WT1 330-348 peptide presented promiscuously across 18 of the 20 tested HLA-II alleles, overcoming single-allele HLA restrictions.
  • WT1-CAR T cells induced specific antitumoral immune responses against leukemic cells in vitro and in vivo in a WT1- and HLA-II-dependent manner.

Cite This Study

Zheng et al. (2026) studied this question.

synapsesocial.com/papers/6a81799af2fb91fc834accdchttps://doi.org/10.1158/2643-3230.bcd-25-0230
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