通过光遗传学工程菌负载 MMP-2 响应性环磷酰胺改善 T 细胞扩增用于抗肿瘤免疫治疗

The efficacy of antitumor immunotherapy is closely associated with the expansion of tumor-infiltrating CD8 + T cells.

However, within the tumor microenvironment, CD8 + T cells often exhibit reduced proliferation due to persistent exposure to tumor antigens. The cytokine IL-2 is a potent growth factor that can drive the expansion of tumor-infiltrating lymphocytes. While its clinical application has been severely limited by systemic toxicity and in vivo instability. To address these challenges, we have developed a dual-responsive system (EcN IL-2 @UCNP/Gel-CTX) leveraging the hypoxic tropisms of E. coli Nissle 1917(EcN).

This system is capable of producing IL-2 in situ upon near-infrared (NIR) irradiation and releasing low-dose cyclophosphamide (CTX) in response to matrix metalloproteinase-2 (MMP-2) in the tumor microenvironment.

The EcN IL-2 @UCNP/Gel-CTX system not only drives the expansion of CD8 + T cells and boost the activity of NK cells but also reduces Treg cell populations, thereby remodeling the immune microenvironment and eliciting robust tumor-specific immune responses in H22 subcutaneous tumors in mice and confers long-term protection against tumor rechallenge by promoting the generation of durable memory T cells.

Our findings provide an both light and tumor microenvironment responsive platform for enhanced cancer immunotherapy.