Sensitive CAR T cells redefine targetable CD70 expression in solid tumors

Solid tumor antigen heterogeneity is a major challenge for cancer immunotherapies, including chimeric antigen receptor (CAR) T cells. Unlike CD19 for B cell malignancies, no target with pan-cellular expression in solid tumors and absence in normal vital cells has been identified. CD70 is a promising candidate, physiologically confined to immune cell subsets and aberrantly expressed in many cancers. We show that heterogeneous CD70 expression in tumors is epigenetically regulated, ranging from high to very low in individual cells, appearing negative by conventional detection methods. Using a highly sensitive CD70 receptor, HLA-independent T cell (HIT) receptor coexpressing CD80 and 4-1BBL for costimulation, we efficiently eliminated CD70-heterogeneous tumors that evade prototypic CAR T cells. These findings provide a potential strategy to treat a broad range of solid tumors.

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Publication Details

Journal
Science
Published
2026-02-26
DOI
https://doi.org/10.1126/science.adv7378
Citations
1
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
24.20
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article

Sensitive CAR T cells redefine targetable CD70 expression in solid tumors

Elisa de Stanchina, Ritesh R. Kotecha, C. S. Leslie, Zeynep Tarcan et al.
1 citations
Science
CAR-T cell therapy research
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Sensitive CAR T cells redefine targetable CD70 expression in solid tumors

Elisa de Stanchina, Ritesh R. Kotecha, C. S. Leslie, Zeynep Tarcan, Tyler Park, Friederike Kogel, Pierre-Jacques Hamard, Chi Ds, Sascha Haubner, Michael Lopez, Michel Sadelain, Jorge Mansilla-Soto, Sarah Nataraj, HuiYong Zhao, Sophie Hanina, Priyam Banerjee, Robert J. Motzer, A. Ari Hakimi, John H. Healey
article en
1 citations

Abstract

Solid tumor antigen heterogeneity is a major challenge for cancer immunotherapies, including chimeric antigen receptor (CAR) T cells. Unlike CD19 for B cell malignancies, no target with pan-cellular expression in solid tumors and absence in normal vital cells has been identified. CD70 is a promising candidate, physiologically confined to immune cell subsets and aberrantly expressed in many cancers. We show that heterogeneous CD70 expression in tumors is epigenetically regulated, ranging from high to very low in individual cells, appearing negative by conventional detection methods. Using a highly sensitive CD70 receptor, HLA-independent T cell (HIT) receptor coexpressing CD80 and 4-1BBL for costimulation, we efficiently eliminated CD70-heterogeneous tumors that evade prototypic CAR T cells. These findings provide a potential strategy to treat a broad range of solid tumors.

ScienceVol. 391(6788)
Memorial Sloan Kettering Cancer Center (US), Cornell University (US), Columbia University Irving Medical Center (US), Rockefeller University (US), Icahn School of Medicine at Mount Sinai (US)
Good health and well-being
Openalex Percentile: Top 1%
CAR-T cell therapy research
24.20
DOISourceOpenAlex
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