The TENSE project engineers natural killer (NK) cells to enhance NK cell infiltration and antitumor activity in solid tumors by overcoming the dense, collagen-rich extracellular matrix

(ECM), contributing to future off-the-shelf adoptive cell therapies (ACT).

Many solid tumors exploit a dysregulated ECM as a physical and immunosuppressive barrier,

blocking immune cell entry and directly suppressing anti-tumor activity. NK cells are among the

most promising candidates for off-the-shelf ACT, but their ability to penetrate collagen-rich

tumors is limited, and the mechanisms underlying ECM-driven NK cell suppression remain

poorly understood, representing a critical bottleneck to achieving clinical efficacy.

TENSE addresses this by genetically engineering NK cells to become ECM-degrading or ECMinsensitive with a focus on collagen-related proteins. The engineered NK cells will be tested in

a range of in vitro and in vivo models to evaluate their infiltration, anti-tumor activity, and

functional responses. Together, these strategies aim to improve NK cell infiltration and

cytotoxicity in collagen-rich solid tumors

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