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Researchers developed an enhanced chick chorioallantoic membrane (CAM) tumor model by grafting engineered murine endothelial cells that form functional connections with the chick vasculature, creating a mammalian vascular interface within human tumor xenografts. The engineered endothelial cells expressing human ICAM-1 significantly improved the recruitment of intravenously delivered human T cells into CAM tumors, overcoming species-specific barriers between human immune cells and avian blood vessels. The platform successfully demonstrated target-dependent T cell activation using bispecific T cell engagers, including the clinically approved drug tarlatamab in small cell lung cancer models.
Why it matters
This platform bridges the gap between simple in vitro systems and complex mouse models, providing a faster, cost-effective preclinical tool for testing cancer immunotherapies that require evaluation of intravenous delivery, immune cell recruitment, and tumor infiltration. The system could accelerate the development and screening of T cell-based therapies before proceeding to more expensive and time-consuming mammalian studies.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
The development of cancer immunotherapies requires preclinical models that capture intravenous delivery, immune cell recruitment and intratumoral T cell activation. Conventional 3D in vitro systems lack perfused vascular networks, whereas mouse models are limited by throughput. The chick chorioallantoic membrane (CAM) assay enables rapid growth of vascularized tumors derived from human cancer cells in ovo, but its application to human T cell-based immunotherapy testing is constrained by CAM-derived vascularization and species-specific barriers between human immune cells and avian endothelium. Here, we establish an endothelial graft-enhanced CAM tumor model that incorporates an immortalized murine endothelial cell line capable of anastomosing with the chick vasculature. This generates a perfused and branched mammalian vascular interface within human tumor xenografts growing on the CAM. Human ICAM-1 expression on the grafted endothelial cells further enhances recruitment of intravenously delivered human T cells into CAM tumors. Using this platform, we demonstrate target-dependent intratumoral T cell activation by bispecific T cell engagers (TCEs) across tumor models, including evaluation of the clinically approved DLL3-targeting TCE tarlatamab in small cell lung cancer models.