A Cytotoxic T Lymphocyte-Inspiring Microscale System for Cancer Immunotherapy

Area of Science:

• Biomaterials Science
• Cancer Immunotherapy
• Nanotechnology

Background:

• Adoptive T cell therapy (ACT) shows promise for solid tumors but faces challenges like cost, T cell heterogeneity, and immunosuppressive tumor microenvironments.
• Current ACT methods are time-consuming, labor-intensive, and financially burdensome, limiting widespread clinical application.

Purpose of the Study:

• To develop a bionic cytotoxic T lymphocyte-inspiring microscale system (CTLiMS) to overcome ACT limitations.
• To mimic the functions of perforin and granzymes using mesoporous silica dioxide microspheres loaded with membrane-disrupting boron clusters (BICs) and monomethyl auristatin E (MMAE).

Main Methods:

• Fabrication of CTLiMS using mesoporous silica dioxide microspheres encapsulating BICs and MMAE.
• In vitro evaluation of CTLiMS anticancer activity, including apoptosis induction and antiproliferative effects.
• In vivo studies in animal models to assess tumor growth repression and immunotherapeutic effects.

Main Results:

• CTLiMS demonstrated potent in vitro anticancer activity, inducing apoptosis and inhibiting proliferation.
• CTLiMS treatment induced immunogenic cell death via Ca2+ and MMAE influx, leading to reactive oxygen species production.
• In vivo studies showed significant tumor growth repression, inhibition of distant tumors, increased immune cell infiltration, and elevated pro-inflammatory cytokines.

Conclusions:

• CTLiMS effectively mimics CTL functions, offering a viable alternative to traditional ACT.
• The bionic strategy shows significant potential for advancing cancer immunotherapy and treating solid tumors.
• This study presents an innovative approach for future development in adoptive T cell therapy.