Extended Data Fig. 1: Structure of the PC13 CAR construct. | Nature Cancer

Extended Data Fig. 1: Structure of the PC13 CAR construct.

From: Hypoxia-responsive CEA-targeted CAR T cells in CEA-positive solid tumors through intraperitoneal or intravenous infusion: a phase 1 trial

Extended Data Fig. 1: Structure of the PC13 CAR construct.

The chimeric antigen receptor (CAR) consists of a humanized scFv directed against the A3 domain of CEACAM5, fused to a BBZ signaling domain (4-1BB co-stimulation and CD3ζ activation). Its expression is driven by five upstream hypoxia-responsive elements (HREs). Under normoxic conditions, HIF-1α protein is rapidly degraded, preventing efficient initiation of CAR gene transcription. Consequently, CAR expression might remain minimal in both circulating T cells and those infiltrating healthy tissues. In contrast, under hypoxic conditions within the tumor microenvironment, HIF-1α stabilization might mediate robust CAR upregulation, leading to rapid surface expression and localized cytotoxic activity.

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