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Engineered NK Exosomes Captured Antigens In Situ for Enhanced Tumor Immunotherapy
Dan Peng1, Lili Cheng1, Junjie Tang1
1School of Biomedical Engineering, Shenzhen Campus of Sun Yat-Sen University, No. 66, Gongchang Road, Guangming District, Shenzhen, Guangdong 518107, China.
ACS Applied Materials & Interfaces
|April 9, 2025
Summary
Engineered natural killer cell-derived exosomes loaded with Raddeanin a and modified with maleimide and mannose enhance tumor immunotherapy by activating innate and adaptive immunity. This approach overcomes the immunosuppressive tumor microenvironment for improved treatment efficacy.
Area of Science:
- Immunology
- Nanotechnology
- Cancer Therapy
Background:
- Natural killer (NK) cells are crucial for tumor immunotherapy but face challenges from the immunosuppressive tumor microenvironment (TME).
- NK cell-derived exosomes (Neo) show potential as antitumor nanocarriers and immunomodulators.
- Existing NK-cell therapies require strategies to overcome TME limitations and enhance efficacy.
Purpose of the Study:
- To engineer NK cell-derived exosomes (Neo) encapsulating Raddeanin a (RA) and modified with maleimide (Mal) and mannose (Man) for enhanced tumor immunotherapy.
- To investigate the ability of engineered Neo (R@Neo-MN) to induce immunogenic cell death and activate the cGAS/STING pathway.
- To evaluate the R@Neo-MN's capacity to promote dendritic cell (DC) maturation and T-cell-mediated adaptive immunity.
Main Methods:
- Design and synthesis of R@Neo-MN, an engineered exosome encapsulating RA and modified with Mal and Man.
- Assessment of R@Neo-MN's NK cell-like antitumor function and induction of immunogenic cell death.
- Analysis of R@Neo-MN's activation of the cGAS/STING pathway, type I interferon (IFN) release, and subsequent immune cell responses.
Main Results:
- R@Neo-MN demonstrated NK cell-like antitumor activity and induced tumor cell death, releasing tumor-associated antigens (TAAs).
- Engineered exosomes activated the cGAS/STING pathway, leading to type I IFN release.
- R@Neo-MN facilitated TAA capture via Mal, targeted DCs via Man, promoted DC maturation, and enhanced cytotoxic T-cell (CTL) responses.
Conclusions:
- Engineered NK cell-derived exosomes (R@Neo-MN) offer a novel strategy for tumor immunotherapy by combining innate and adaptive immune activation.
- This approach overcomes TME limitations and enhances antitumor immunity through targeted delivery and immune stimulation.
- R@Neo-MN holds promise for developing more effective cancer immunotherapies by harnessing exosome-based drug delivery and immune modulation.
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