Evaluation of the antitumor effect of neoantigen peptide vaccines derived from the translatome of lung cancer
Emerging evidence suggests that tumor-specific neoantigens are ideal targets for cancer immunotherapy. However, how to predict tumor neoantigens based on translatome data remains obscure. Through the extraction of ribosome-nascent chain complexes (RNCs) from LLC cells, followed by RNC-mRNA extractio...
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| Veröffentlicht in: | Cancer Immunology, Immunotherapy : CII Immunotherapy : CII, 2024-05, Vol.73 (7), p.129, Article 129 |
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| container_title | Cancer Immunology, Immunotherapy : CII |
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| creator | Lian, Fenbao Yang, Haitao Hong, Rujun Xu, Hang Yu, Tingting Sun, Gang Zheng, Guanying Xie, Baosong |
| description | Emerging evidence suggests that tumor-specific neoantigens are ideal targets for cancer immunotherapy. However, how to predict tumor neoantigens based on translatome data remains obscure. Through the extraction of ribosome-nascent chain complexes (RNCs) from LLC cells, followed by RNC-mRNA extraction, RNC-mRNA sequencing, and comprehensive bioinformatic analysis, we successfully identified proteins undergoing translatome and exhibiting mutations in the cells. Subsequently, novel antigens identification was analyzed by the interaction between their high affinity and the Major Histocompatibility Complex (MHC). Neoantigens immunogenicity was analyzed by enzyme-linked immunospot assay (ELISpot). Finally, in vivo experiments in mice were conducted to evaluate the antitumor effects of translatome-derived neoantigen peptides on lung cancer. The results showed that ten neoantigen peptides were identified and synthesized by translatome data from LLC cells; 8 out of the 10 neoantigens had strong immunogenicity. The neoantigen peptide vaccine group exhibited significant tumor growth inhibition effect. In conclusion, neoantigen peptide vaccine derived from the translatome of lung cancer exhibited significant tumor growth inhibition effect. |
| doi_str_mv | 10.1007/s00262-024-03670-0 |
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However, how to predict tumor neoantigens based on translatome data remains obscure. Through the extraction of ribosome-nascent chain complexes (RNCs) from LLC cells, followed by RNC-mRNA extraction, RNC-mRNA sequencing, and comprehensive bioinformatic analysis, we successfully identified proteins undergoing translatome and exhibiting mutations in the cells. Subsequently, novel antigens identification was analyzed by the interaction between their high affinity and the Major Histocompatibility Complex (MHC). Neoantigens immunogenicity was analyzed by enzyme-linked immunospot assay (ELISpot). Finally, in vivo experiments in mice were conducted to evaluate the antitumor effects of translatome-derived neoantigen peptides on lung cancer. The results showed that ten neoantigen peptides were identified and synthesized by translatome data from LLC cells; 8 out of the 10 neoantigens had strong immunogenicity. The neoantigen peptide vaccine group exhibited significant tumor growth inhibition effect. In conclusion, neoantigen peptide vaccine derived from the translatome of lung cancer exhibited significant tumor growth inhibition effect.</description><identifier>ISSN: 1432-0851</identifier><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-024-03670-0</identifier><identifier>PMID: 38744688</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Animals ; Antigens ; Antigens, Neoplasm - immunology ; Antitumor activity ; Cancer immunotherapy ; Cancer Research ; Cancer Vaccines - immunology ; Cell Line, Tumor ; Enzyme-linked immunosorbent assay ; Female ; Growth inhibition ; Humans ; Immunogenicity ; Immunology ; Immunotherapy - methods ; Lung cancer ; Lung Neoplasms - immunology ; Lung Neoplasms - therapy ; Major histocompatibility complex ; Medicine ; Medicine & Public Health ; Mice ; Mice, Inbred C57BL ; mRNA ; Neoantigens ; Oncology ; Peptides ; Protein Subunit Vaccines ; Tumors ; Vaccines ; Vaccines, Subunit - immunology</subject><ispartof>Cancer Immunology, Immunotherapy : CII, 2024-05, Vol.73 (7), p.129, Article 129</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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However, how to predict tumor neoantigens based on translatome data remains obscure. Through the extraction of ribosome-nascent chain complexes (RNCs) from LLC cells, followed by RNC-mRNA extraction, RNC-mRNA sequencing, and comprehensive bioinformatic analysis, we successfully identified proteins undergoing translatome and exhibiting mutations in the cells. Subsequently, novel antigens identification was analyzed by the interaction between their high affinity and the Major Histocompatibility Complex (MHC). Neoantigens immunogenicity was analyzed by enzyme-linked immunospot assay (ELISpot). Finally, in vivo experiments in mice were conducted to evaluate the antitumor effects of translatome-derived neoantigen peptides on lung cancer. The results showed that ten neoantigen peptides were identified and synthesized by translatome data from LLC cells; 8 out of the 10 neoantigens had strong immunogenicity. The neoantigen peptide vaccine group exhibited significant tumor growth inhibition effect. 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| subjects | Animals Antigens Antigens, Neoplasm - immunology Antitumor activity Cancer immunotherapy Cancer Research Cancer Vaccines - immunology Cell Line, Tumor Enzyme-linked immunosorbent assay Female Growth inhibition Humans Immunogenicity Immunology Immunotherapy - methods Lung cancer Lung Neoplasms - immunology Lung Neoplasms - therapy Major histocompatibility complex Medicine Medicine & Public Health Mice Mice, Inbred C57BL mRNA Neoantigens Oncology Peptides Protein Subunit Vaccines Tumors Vaccines Vaccines, Subunit - immunology |
| title | Evaluation of the antitumor effect of neoantigen peptide vaccines derived from the translatome of lung cancer |
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