التفاصيل البيبلوغرافية
| العنوان: |
Chimeric RNAs reveal putative neoantigen peptides for developing tumor vaccines for breast cancer. |
| المؤلفون: |
Mistretta, Brandon, Rankothgedera, Sakuni, Castillo, Micah, Rao, Mitchell, Holloway, Kimberly, Bhardwaj, Anjana, El Noafal, Maha, Albarracin, Constance, El-Zein, Randa, Rezaei, Hengameh, Xiaoping Su, Akbani, Rehan, Xiaoshan M. Shao, Czerniecki, Brian J., Karchin, Rachel, Bedrosian, Isabelle, Gunaratne, Preethi H. |
| المصدر: |
Frontiers in Immunology; 2023, p01-15, 15p |
| مصطلحات موضوعية: |
CANCER vaccines, CHIMERIC proteins, VACCINE development, BREAST tumors, BREAST cancer, PEPTIDES |
| مستخلص: |
Introduction: We present here a strategy to identify immunogenic neoantigen candidates from unique amino acid sequences at the junctions of fusion proteins which can serve as targets in the development of tumor vaccines for the treatment of breastcancer. Method: We mined the sequence reads of breast tumor tissue that are usually discarded as discordant paired-end reads and discovered cancer specific fusion transcripts using tissue from cancer free controls as reference. Binding affinity predictions of novel peptide sequences crossing the fusion junction were analyzed by the MHC Class I binding predictor, MHCnuggets. CD8+ T cell responses against the 15 peptides were assessed through in vitro Enzyme Linked Immunospot (ELISpot). Results: We uncovered 20 novel fusion transcripts from 75 breast tumors of 3 subtypes: TNBC, HER2+, and HR+. Of these, the NSFP1-LRRC37A2 fusion transcript was selected for further study. The 3833 bp chimeric RNA predicted by the consensus fusion junction sequence is consistent with a read-through transcription of the 5'-gene NSFP1-Pseudo gene NSFP1 (NSFtruncation at exon 12/13) followed by trans-splicing to connect withLRRC37A2 located immediately 3' through exon 1/2. A total of 15 different 8-mer neoantigen peptides discovered from the NSFP1 and LRRC37A2 truncations were predicted to bind to a total of 35 unique MHC class I alleles with a binding affinity of IC50<500nM.); 1 of which elicited a robust immune response. Conclusion: Our data provides a framework to identify immunogenic neoantigen candidates from fusion transcripts and suggests a potential vaccine strategy to target the immunogenic neopeptides in patients with tumors carrying the NSFP1-LRRC37A2 fusion. [ABSTRACT FROM AUTHOR] |
|
Copyright of Frontiers in Immunology is the property of Frontiers Media S.A. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder