Leveraging mRNA technology for antigen based immuno-oncology therapies
The application of messenger RNA (mRNA) technology in antigen-based immuno-oncology therapies represents a significant advancement in cancer treatment. Cancer vaccines are an effective combinatorial partner to sensitize the host immune system to the tumor and boost the efficacy of immune therapies....
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| Format: | Article |
| Language: | English |
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BMJ Publishing Group
2025-01-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/1/e010569.full |
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| author | Wei Zheng Michele Ceccarelli Charalampos S Floudas Siranush Sarkizova |
| author_facet | Wei Zheng Michele Ceccarelli Charalampos S Floudas Siranush Sarkizova |
| author_sort | Wei Zheng |
| collection | DOAJ |
| description | The application of messenger RNA (mRNA) technology in antigen-based immuno-oncology therapies represents a significant advancement in cancer treatment. Cancer vaccines are an effective combinatorial partner to sensitize the host immune system to the tumor and boost the efficacy of immune therapies. Selecting suitable tumor antigens is the key step to devising effective vaccinations and amplifying the immune response. Tumor neoantigens are de novo epitopes derived from somatic mutations, avoiding T-cell central tolerance of self-epitopes and inducing immune responses to tumors. The identification and prioritization of patient-specific tumor neoantigens are based on advanced computational algorithms taking advantage of the profiling with next-generation sequencing considering factors involved in human leukocyte antigen (HLA)-peptide-T-cell receptor (TCR) complex formation, including peptide presentation, HLA-peptide affinity, and TCR recognition. This review discusses the development and clinical application of mRNA vaccines in oncology, with a particular focus on recent clinical trials and the computational workflows and methodologies for identifying both shared and individual antigens. While this review centers on therapeutic mRNA vaccines targeting existing tumors, it does not cover preventative vaccines. Preclinical experimental validations are crucial in cancer vaccine development, but we emphasize the computational approaches that facilitate neoantigen selection and design, highlighting their role in advancing mRNA vaccine development. The versatility and rapid development potential of mRNA make it an ideal platform for personalized neoantigen immunotherapy. We explore various strategies for antigen target identification, including tumor-associated and tumor-specific antigens and the computational tools used to predict epitopes capable of eliciting strong immune responses. We address key design considerations for enhancing the immunogenicity and stability of mRNA vaccines, as well as emerging trends and challenges in the field. This comprehensive overview highlights the therapeutic potential of mRNA-based cancer vaccines and underscores ongoing research efforts aimed at optimizing these therapies for improved clinical outcomes. |
| format | Article |
| id | doaj-art-f4b1aacb8cdc4692a478306826292620 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-f4b1aacb8cdc4692a4783068262926202025-01-23T09:35:09ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-01-0113110.1136/jitc-2024-010569Leveraging mRNA technology for antigen based immuno-oncology therapiesWei Zheng0Michele Ceccarelli1Charalampos S Floudas2Siranush Sarkizova3Department of Critical Care Medicine, Zhuhai People’s Hospital, Zhuhai, Guangdong Province, China22 Istituto di Ricerche Genetiche G. Salvatore, Biogem s.c.ar.l, 83031, Ariano Irpino, Italy3National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA2 Moderna, Inc, Cambridge, Massachusetts, USAThe application of messenger RNA (mRNA) technology in antigen-based immuno-oncology therapies represents a significant advancement in cancer treatment. Cancer vaccines are an effective combinatorial partner to sensitize the host immune system to the tumor and boost the efficacy of immune therapies. Selecting suitable tumor antigens is the key step to devising effective vaccinations and amplifying the immune response. Tumor neoantigens are de novo epitopes derived from somatic mutations, avoiding T-cell central tolerance of self-epitopes and inducing immune responses to tumors. The identification and prioritization of patient-specific tumor neoantigens are based on advanced computational algorithms taking advantage of the profiling with next-generation sequencing considering factors involved in human leukocyte antigen (HLA)-peptide-T-cell receptor (TCR) complex formation, including peptide presentation, HLA-peptide affinity, and TCR recognition. This review discusses the development and clinical application of mRNA vaccines in oncology, with a particular focus on recent clinical trials and the computational workflows and methodologies for identifying both shared and individual antigens. While this review centers on therapeutic mRNA vaccines targeting existing tumors, it does not cover preventative vaccines. Preclinical experimental validations are crucial in cancer vaccine development, but we emphasize the computational approaches that facilitate neoantigen selection and design, highlighting their role in advancing mRNA vaccine development. The versatility and rapid development potential of mRNA make it an ideal platform for personalized neoantigen immunotherapy. We explore various strategies for antigen target identification, including tumor-associated and tumor-specific antigens and the computational tools used to predict epitopes capable of eliciting strong immune responses. We address key design considerations for enhancing the immunogenicity and stability of mRNA vaccines, as well as emerging trends and challenges in the field. This comprehensive overview highlights the therapeutic potential of mRNA-based cancer vaccines and underscores ongoing research efforts aimed at optimizing these therapies for improved clinical outcomes.https://jitc.bmj.com/content/13/1/e010569.full |
| spellingShingle | Wei Zheng Michele Ceccarelli Charalampos S Floudas Siranush Sarkizova Leveraging mRNA technology for antigen based immuno-oncology therapies Journal for ImmunoTherapy of Cancer |
| title | Leveraging mRNA technology for antigen based immuno-oncology therapies |
| title_full | Leveraging mRNA technology for antigen based immuno-oncology therapies |
| title_fullStr | Leveraging mRNA technology for antigen based immuno-oncology therapies |
| title_full_unstemmed | Leveraging mRNA technology for antigen based immuno-oncology therapies |
| title_short | Leveraging mRNA technology for antigen based immuno-oncology therapies |
| title_sort | leveraging mrna technology for antigen based immuno oncology therapies |
| url | https://jitc.bmj.com/content/13/1/e010569.full |
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