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Updated: May 12, 2025

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Development and optimization of Eva1 (MPZL2) targeting chimeric antigen receptor T cells

Masahide Osaki1, Seitaro Terakura2, Shiho Hirano1

  • 1Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Journal for Immunotherapy of Cancer
|May 9, 2025
PubMed
Abstract

Insights

Chimeric antigen receptor T (CAR-T) cell therapy targeting Epithelial V-like antigen 1 (Eva1) shows promise for solid tumors. Optimized Eva1CAR-T cells demonstrated significant efficacy in preclinical models, suggesting potential for treating various Eva1-positive solid cancers.

Area of Science:

  • Immunotherapy
  • Oncology
  • Cellular Engineering

Background:

  • Chimeric antigen receptor T (CAR-T) cell therapy is established for hematologic malignancies but not solid tumors.
  • Epithelial V-like antigen 1 (Eva1), a surface protein on various tumor cells, is a potential target for solid tumor therapy.

Purpose of the Study:

  • To develop and optimize CAR-T cells targeting Epithelial V-like antigen 1 (Eva1) for solid tumors.
  • To evaluate the efficacy and safety of Eva1-targeted CAR-T cells in preclinical models.

Main Methods:

  • Humanized single-chain variable fragment sequences were generated against Eva1.
  • Six humanized Eva1CAR-T cell constructs were created and optimized for specificity and proliferation.
  • In vitro and in vivo xenograft mouse models were used to assess therapeutic efficacy and cytokine release.

Main Results:

  • Eva1 expression was confirmed on various tumor cell lines, with weak expression on normal monocytes.
  • Optimized Eva1CAR-T cells with short spacer domains and specific intracellular domains showed enhanced efficacy.
  • A single dose of humanized Eva1CAR-T cells demonstrated significant therapeutic effects in lung and pancreatic cancer models.

Conclusions:

  • Humanized Eva1CAR-T cells exhibit promising therapeutic potential for Eva1-positive solid tumors.
  • Further investigation into on-target/off-tumor effects on normal tissues is warranted.
Keywords:
Adoptive cell therapy - ACTChimeric antigen receptor - CARLung CancerSolid tumor

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