A cancer vaccine approach for personalized treatment of Lynch Syndrome
| العنوان: | A cancer vaccine approach for personalized treatment of Lynch Syndrome |
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| المؤلفون: | Vasumathi Kode, Yogesh Mistry, Lakshmi Mahadevan, Snigdha Majumder, Karunakaran Coral, Papia Chakraborty, Bharti Mittal, Arati Khanna-Gupta, Malini Manoharan, Priyanka Shah, Sakthivel Murugan Sm, Rakshit Shah, Jisha Elias, Ravi Gupta, Anjali Kumari, Amitabha Chaudhuri |
| المصدر: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-14 (2018) |
| بيانات النشر: | Springer Science and Business Media LLC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Adult, 0301 basic medicine, T cell, DNA Mutational Analysis, lcsh:Medicine, Epitopes, T-Lymphocyte, CD8-Positive T-Lymphocytes, MLH1, medicine.disease_cause, Cancer Vaccines, Article, Young Adult, 03 medical and health sciences, Immunogenicity, Vaccine, 0302 clinical medicine, Germline mutation, Antigen, Antigens, Neoplasm, Exome Sequencing, medicine, Humans, Precision Medicine, lcsh:Science, Child, Frameshift Mutation, Germ-Line Mutation, Aged, Immune Evasion, Aged, 80 and over, Mutation, Multidisciplinary, Sequence Analysis, RNA, business.industry, lcsh:R, Middle Aged, medicine.disease, Colorectal Neoplasms, Hereditary Nonpolyposis, Lynch syndrome, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Vaccines, Subunit, Cancer research, lcsh:Q, DNA mismatch repair, Cancer vaccine, Neoplasm Recurrence, Local, MutL Protein Homolog 1, business |
| الوصف: | Lynch syndrome (LS) is a cancer predisposition disorder wherein patients have a 70–80% lifetime risk of developing colorectal cancers (CRC). Finding germline mutations in predisposing genes allows for risk assessment of CRC development. Here we report a germline heterozygous frame-shift mutation in the mismatch repair MLH1 gene which was identified in members of two unrelated LS families. Since defects in DNA mismatch repair genes generate frame-shift mutations giving rise to highly immunogenic neoepitopes, we postulated that vaccination with these mutant peptide antigens could offer promising treatment options to LS patients. To this end we performed whole-exome and RNA seq analysis on the blood and tumour samples from an LS-CRC patient, and used our proprietary neoepitope prioritization pipeline OncoPeptVAC to select peptides, and confirm their immunogenicity in an ex vivo CD8+ T cell activation assay. Three neoepitopes derived from the tumour of this patient elicited a potent CD8+ T cell response. Furthermore, analysis of the tumour-associated immune infiltrate revealed CD8+ T cells expressing low levels of activation markers, suggesting mechanisms of immune suppression at play in this relapsed tumour. Taken together, our study paves the way towards development of a cancer vaccine to treat or delay the onset/relapse of LS-CRC. |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ec7da21f96bc9c0302e7f49a733ed1c0 https://doi.org/10.1038/s41598-018-30466-x |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....ec7da21f96bc9c0302e7f49a733ed1c0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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