ArticleCytotherapy2026
Hypoxia during GPC2-CAR T-cell manufacturing compromises cell expansion and cytotoxic capacity.
Article in Cytotherapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND AND
aimHypoxia is a hallmark of the solid tumor microenvironment and is known to impair CAR T-cell function. In order to condition CAR T-cells to this microenvironment during manufacturing, we evaluated whether varying oxygen tension during the manufacturing of GPC2-CAR T-cells improves cellular characteristics and function against neuroblastoma.
methodsCell products were produced over 8-9 days under normoxic (21% oxygen), transitional (21%, then transitioned to 1% on Day 2), or maintained hypoxic conditions (1% from Day 0 onward). RNA-sequencing, metabolic assays, phenotyping, and functional studies were performed.
resultsSustained hypoxia induced universal changes in CAR T-cells, including increased surface CAR expression, enrichment of T
conclusionsThese findings indicate that oxygen tension substantially alters both CAR T-cell products and tumor cell state. Sustained hypoxic manufacturing does not improve GPC2-CAR T-cell efficacy and instead compromises yield and antitumor function. Thus, for this GPC2-CAR T-cell product, normoxic manufacturing remains the most favorable approach for clinical translation.
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