Fragment Autoantigens Stimulated T‐Cell‐Immunotherapy (FAST) as a Fast Autologous Cancer Vaccine
Abstract Tumor cells often down‐regulate antigen presentation and mount an immunosuppressive microenvironment, hindering successful cancer immunotherapy and vaccine development. Additionally, due to genomic instability, tumor cells are usually heterogeneous and constantly evolving. Therefore, vaccin...
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Wiley
2025-07-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202502937 |
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| author | Yuan Li Huiqin Chen Qiaofeng Shen Yingshuang Liu Pingping Li Yuqi Ma Yugang Wang Shengkai Li Xueqing Yan Liyu Liu Jianwei Shuai Min Wu Qi Ouyang Feng‐Ming (Spring) Kong Gen Yang |
| author_facet | Yuan Li Huiqin Chen Qiaofeng Shen Yingshuang Liu Pingping Li Yuqi Ma Yugang Wang Shengkai Li Xueqing Yan Liyu Liu Jianwei Shuai Min Wu Qi Ouyang Feng‐Ming (Spring) Kong Gen Yang |
| author_sort | Yuan Li |
| collection | DOAJ |
| description | Abstract Tumor cells often down‐regulate antigen presentation and mount an immunosuppressive microenvironment, hindering successful cancer immunotherapy and vaccine development. Additionally, due to genomic instability, tumor cells are usually heterogeneous and constantly evolving. Therefore, vaccines need broad antigen coverage and rapid preparation. Here, a personalized whole tumor cell vaccine (TCV), termed fragment autoantigens stimulated T‐cell‐immunotherapy (FAST) is developed. In 7 h, tumor cells are treated with irradiation and cryoablation. Personalized fragmented antigens (FAs) from these treated cells are used as TCVs. In breast, colon, and melanoma mouse models, FAST achieved significant tumor regression, less metastasis, and longer survival. Notably, FAST outperforms other advanced TCVs, especially in curbing metastasis. Mechanistically, FAs activate efficient, broad‐spectrum antigen presentation due to upregulation of immunogenic cell death, MHC‐I, and damage‐associated molecular patterns. Concurrently, FAST also enhances anti‐tumor immunity by reshaping immune microenvironments. Analysis of clinical data shows FAST‐associated proteins have prognostic and therapeutic value in patients with liver, stomach, rectal cancers, and melanoma. These results suggest FAST has high anti‐tumor efficacy and potential as a personalized TCV platform. The relevant clinical trial NCT06756295 is under initiation with approval of ethics. |
| format | Article |
| id | doaj-art-5d2c756d2ee245f28cf341a09da174b0 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-5d2c756d2ee245f28cf341a09da174b02025-08-20T03:04:57ZengWileyAdvanced Science2198-38442025-07-011226n/an/a10.1002/advs.202502937Fragment Autoantigens Stimulated T‐Cell‐Immunotherapy (FAST) as a Fast Autologous Cancer VaccineYuan Li0Huiqin Chen1Qiaofeng Shen2Yingshuang Liu3Pingping Li4Yuqi Ma5Yugang Wang6Shengkai Li7Xueqing Yan8Liyu Liu9Jianwei Shuai10Min Wu11Qi Ouyang12Feng‐Ming (Spring) Kong13Gen Yang14State Key Laboratory of Nuclear Physics and Technology School of Physics Peking University Beijing 100871 ChinaWenzhou Institute University of Chinese Academy of Sciences Wenzhou 352001 ChinaWenzhou Institute University of Chinese Academy of Sciences Wenzhou 352001 ChinaWenzhou Institute University of Chinese Academy of Sciences Wenzhou 352001 ChinaWenzhou Institute University of Chinese Academy of Sciences Wenzhou 352001 ChinaState Key Laboratory of Nuclear Physics and Technology School of Physics Peking University Beijing 100871 ChinaState Key Laboratory of Nuclear Physics and Technology School of Physics Peking University Beijing 100871 ChinaDepartment of Physics Princeton University Princeton NJ 08544 USAState Key Laboratory of Nuclear Physics and Technology School of Physics Peking University Beijing 100871 ChinaWenzhou Institute University of Chinese Academy of Sciences Wenzhou 352001 ChinaWenzhou Institute University of Chinese Academy of Sciences Wenzhou 352001 ChinaWenzhou Institute University of Chinese Academy of Sciences Wenzhou 352001 ChinaCenter for Quantitative Biology Peking University Beijing 100871 ChinaDepartment of Clinical Oncology University of Hong Kong Hong Kong 999077 ChinaState Key Laboratory of Nuclear Physics and Technology School of Physics Peking University Beijing 100871 ChinaAbstract Tumor cells often down‐regulate antigen presentation and mount an immunosuppressive microenvironment, hindering successful cancer immunotherapy and vaccine development. Additionally, due to genomic instability, tumor cells are usually heterogeneous and constantly evolving. Therefore, vaccines need broad antigen coverage and rapid preparation. Here, a personalized whole tumor cell vaccine (TCV), termed fragment autoantigens stimulated T‐cell‐immunotherapy (FAST) is developed. In 7 h, tumor cells are treated with irradiation and cryoablation. Personalized fragmented antigens (FAs) from these treated cells are used as TCVs. In breast, colon, and melanoma mouse models, FAST achieved significant tumor regression, less metastasis, and longer survival. Notably, FAST outperforms other advanced TCVs, especially in curbing metastasis. Mechanistically, FAs activate efficient, broad‐spectrum antigen presentation due to upregulation of immunogenic cell death, MHC‐I, and damage‐associated molecular patterns. Concurrently, FAST also enhances anti‐tumor immunity by reshaping immune microenvironments. Analysis of clinical data shows FAST‐associated proteins have prognostic and therapeutic value in patients with liver, stomach, rectal cancers, and melanoma. These results suggest FAST has high anti‐tumor efficacy and potential as a personalized TCV platform. The relevant clinical trial NCT06756295 is under initiation with approval of ethics.https://doi.org/10.1002/advs.202502937immunotherapyradiotherapywhole tumor cell vaccines |
| spellingShingle | Yuan Li Huiqin Chen Qiaofeng Shen Yingshuang Liu Pingping Li Yuqi Ma Yugang Wang Shengkai Li Xueqing Yan Liyu Liu Jianwei Shuai Min Wu Qi Ouyang Feng‐Ming (Spring) Kong Gen Yang Fragment Autoantigens Stimulated T‐Cell‐Immunotherapy (FAST) as a Fast Autologous Cancer Vaccine Advanced Science immunotherapy radiotherapy whole tumor cell vaccines |
| title | Fragment Autoantigens Stimulated T‐Cell‐Immunotherapy (FAST) as a Fast Autologous Cancer Vaccine |
| title_full | Fragment Autoantigens Stimulated T‐Cell‐Immunotherapy (FAST) as a Fast Autologous Cancer Vaccine |
| title_fullStr | Fragment Autoantigens Stimulated T‐Cell‐Immunotherapy (FAST) as a Fast Autologous Cancer Vaccine |
| title_full_unstemmed | Fragment Autoantigens Stimulated T‐Cell‐Immunotherapy (FAST) as a Fast Autologous Cancer Vaccine |
| title_short | Fragment Autoantigens Stimulated T‐Cell‐Immunotherapy (FAST) as a Fast Autologous Cancer Vaccine |
| title_sort | fragment autoantigens stimulated t cell immunotherapy fast as a fast autologous cancer vaccine |
| topic | immunotherapy radiotherapy whole tumor cell vaccines |
| url | https://doi.org/10.1002/advs.202502937 |
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