Kim, Gi Beom Kim, Seonghyun Hwang, Yeong Ha Kim, Seohyun Lee, Inkyu Kim, Seong A. Goo, Jiyoung Yang, Yoosoo Jeong, Cherlhyun Nam, Gi-Hoon Kim, In-San 2024-01-19T09:00:53Z 2024-01-19T09:00:53Z 2023-06-15 2023-09 1613-6810 https://pubs.kist.re.kr/handle/201004/113363 In this study, extracellular vesicles (EVs) are reimagined as more than just a cellular waste disposal system and are repurposed for cancer immunotherapy. Potent oncolytic EVs (bRSVF-EVs) loaded with misfolded proteins (MPs) are engineered, which are typically considered cellular debris. By impairing lysosomal function using bafilomycin A1 and expressing the respiratory syncytial virus F protein, a viral fusogen, MPs are successfully loaded into the EVs expressing RSVF. bRSVF-EVs preferentially transplant a xenogeneic antigen onto cancer cell membranes in a nucleolin-dependent manner, triggering an innate immune response. Furthermore, bRSVF-EV-mediated direct delivery of MPs into the cancer cell cytoplasm initiates endoplasmic reticulum stress and immunogenic cell death (ICD). This mechanism of action leads to substantial antitumor immune responses in murine tumor models. Importantly, when combined with PD-1 blockade, bRSVF-EV treatment elicits robust antitumor immunity, resulting in prolonged survival and complete remission in some cases. Overall, the findings demonstrate that utilizing tumor-targeting oncolytic EVs for direct cytoplasmic delivery of MPs to induce ICD in cancer cells represents a promising approach for enhancing durable antitumor immunity. English Wiley - V C H Verlag GmbbH & Co. Harnessing Oncolytic Extracellular Vesicles for Tumor Cell-Preferential Cytoplasmic Delivery of Misfolded Proteins for Cancer Immunotherapy Article 10.1002/smll.202300527 1 Small, v.19, no.37 Small 19 37 Y scie scopus 000994047700001 2-s2.0-85159875115 Chemistry, Multidisciplinary Chemistry, Physical Nanoscience & Nanotechnology Materials Science, Multidisciplinary Physics, Applied Physics, Condensed Matter Chemistry Science & Technology - Other Topics Materials Science Physics Article NUCLEOLIN PROGNOSIS EXOSOMES APTAMER cancer immunotherapy endoplasmic reticulum (ER) stress extracellular vesicles immunogenic cell death misfolded proteins respiratory syncytial virus F proteins xenogenization