Novel mRNA adjuvant ImmunER enhances prostate cancer tumor-associated antigen mRNA therapy via augmenting T cell activity
Prostate cancer (PCa) is characterized as a “cold tumor” with limited immune responses, rendering the tumor resistant to immune checkpoint inhibitors (ICI). Therapeutic messenger RNA (mRNA) vaccines have emerged as a promising strategy to overcome this challenge by enhancing immune reactivity and si...
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| Format: | Article |
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Taylor & Francis Group
2024-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2373526 |
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| author | Zhen Xu Ze-Xiu Xiao Jing Wang Hao-Wei Qiu Fei Cao Shi-Qiang Zhang Yuan-Dong Xu Han-Qi Lei Heng Xia Yun-Ru He Gao-Feng Zha Jun Pang |
| author_facet | Zhen Xu Ze-Xiu Xiao Jing Wang Hao-Wei Qiu Fei Cao Shi-Qiang Zhang Yuan-Dong Xu Han-Qi Lei Heng Xia Yun-Ru He Gao-Feng Zha Jun Pang |
| author_sort | Zhen Xu |
| collection | DOAJ |
| description | Prostate cancer (PCa) is characterized as a “cold tumor” with limited immune responses, rendering the tumor resistant to immune checkpoint inhibitors (ICI). Therapeutic messenger RNA (mRNA) vaccines have emerged as a promising strategy to overcome this challenge by enhancing immune reactivity and significantly boosting anti-tumor efficacy. In our study, we synthesized Tetra, an mRNA vaccine mixed with multiple tumor-associated antigens, and ImmunER, an immune-enhancing adjuvant, aiming to induce potent anti-tumor immunity. ImmunER exhibited the capacity to promote dendritic cells (DCs) maturation, enhance DCs migration, and improve antigen presentation at both cellular and animal levels. Moreover, Tetra, in combination with ImmunER, induced a transformation of bone marrow-derived dendritic cells (BMDCs) to cDC1-CCL22 and up-regulated the JAK-STAT1 pathway, promoting the release of IL-12, TNF-α, and other cytokines. This cascade led to enhanced proliferation and activation of T cells, resulting in effective killing of tumor cells. In vivo experiments further revealed that Tetra + ImmunER increased CD8+T cell infiltration and activation in RM-1-PSMA tumor tissues. In summary, our findings underscore the promising potential of the integrated Tetra and ImmunER mRNA-LNP therapy for robust anti-tumor immunity in PCa. |
| format | Article |
| id | doaj-art-cbd29fbd3fa84d29b98360b4a443d88f |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-cbd29fbd3fa84d29b98360b4a443d88f2024-12-03T13:49:34ZengTaylor & Francis GroupOncoImmunology2162-402X2024-12-0113110.1080/2162402X.2024.2373526Novel mRNA adjuvant ImmunER enhances prostate cancer tumor-associated antigen mRNA therapy via augmenting T cell activityZhen Xu0Ze-Xiu Xiao1Jing Wang2Hao-Wei Qiu3Fei Cao4Shi-Qiang Zhang5Yuan-Dong Xu6Han-Qi Lei7Heng Xia8Yun-Ru He9Gao-Feng Zha10Jun Pang11Department of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, ChinaDrug Discovery Center, Shenzhen MagicRNA Biotech, Shenzhen, Guangdong, ChinaDrug Discovery Center, Shenzhen MagicRNA Biotech, Shenzhen, Guangdong, ChinaScientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, ChinaDepartment of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, ChinaDepartment of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, ChinaDepartment of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, ChinaDepartment of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, ChinaScientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, ChinaScientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, ChinaDrug Discovery Center, Shenzhen MagicRNA Biotech, Shenzhen, Guangdong, ChinaDepartment of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, ChinaProstate cancer (PCa) is characterized as a “cold tumor” with limited immune responses, rendering the tumor resistant to immune checkpoint inhibitors (ICI). Therapeutic messenger RNA (mRNA) vaccines have emerged as a promising strategy to overcome this challenge by enhancing immune reactivity and significantly boosting anti-tumor efficacy. In our study, we synthesized Tetra, an mRNA vaccine mixed with multiple tumor-associated antigens, and ImmunER, an immune-enhancing adjuvant, aiming to induce potent anti-tumor immunity. ImmunER exhibited the capacity to promote dendritic cells (DCs) maturation, enhance DCs migration, and improve antigen presentation at both cellular and animal levels. Moreover, Tetra, in combination with ImmunER, induced a transformation of bone marrow-derived dendritic cells (BMDCs) to cDC1-CCL22 and up-regulated the JAK-STAT1 pathway, promoting the release of IL-12, TNF-α, and other cytokines. This cascade led to enhanced proliferation and activation of T cells, resulting in effective killing of tumor cells. In vivo experiments further revealed that Tetra + ImmunER increased CD8+T cell infiltration and activation in RM-1-PSMA tumor tissues. In summary, our findings underscore the promising potential of the integrated Tetra and ImmunER mRNA-LNP therapy for robust anti-tumor immunity in PCa.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2373526Immunotherapylipid nanoparticlesmRNA vaccineprostate cancertumor-associated antigens |
| spellingShingle | Zhen Xu Ze-Xiu Xiao Jing Wang Hao-Wei Qiu Fei Cao Shi-Qiang Zhang Yuan-Dong Xu Han-Qi Lei Heng Xia Yun-Ru He Gao-Feng Zha Jun Pang Novel mRNA adjuvant ImmunER enhances prostate cancer tumor-associated antigen mRNA therapy via augmenting T cell activity OncoImmunology Immunotherapy lipid nanoparticles mRNA vaccine prostate cancer tumor-associated antigens |
| title | Novel mRNA adjuvant ImmunER enhances prostate cancer tumor-associated antigen mRNA therapy via augmenting T cell activity |
| title_full | Novel mRNA adjuvant ImmunER enhances prostate cancer tumor-associated antigen mRNA therapy via augmenting T cell activity |
| title_fullStr | Novel mRNA adjuvant ImmunER enhances prostate cancer tumor-associated antigen mRNA therapy via augmenting T cell activity |
| title_full_unstemmed | Novel mRNA adjuvant ImmunER enhances prostate cancer tumor-associated antigen mRNA therapy via augmenting T cell activity |
| title_short | Novel mRNA adjuvant ImmunER enhances prostate cancer tumor-associated antigen mRNA therapy via augmenting T cell activity |
| title_sort | novel mrna adjuvant immuner enhances prostate cancer tumor associated antigen mrna therapy via augmenting t cell activity |
| topic | Immunotherapy lipid nanoparticles mRNA vaccine prostate cancer tumor-associated antigens |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2373526 |
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