Intracellular expression of a chimeric antigen reverses resistance to cancer immunotherapy
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE245743 | GEO | 2024/10/16
REPOSITORIES: GEO
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Project description:RNA Sequencing of the murine breast cancer cell line 4T1 and of the murine melanoma cell line B16-ova was carried out with the aim of establishing the complete transcriptome of these cell lines. Because these are cancer cells and we expect a lot of aberrant splicing, we carried out de novo assembly (genome guided) of the transcripts. We also ran deep Mass Spectrometry proteomics analysis on the same cell lines, aiming to determine which aberrant transcripts carry over to the protein expression level. Further, we tested these cancer specific protein epitopes (putative neoantigens) for immunogenicity using mouse models. Finally, the putative neoantigens that showed good immunogenic potential were used in tumor growth control experiments with mice engrafted with the two tumor cell lines. In these experiments we tested whether cancer vaccines based on individual neoantigen peptides (MHC-I) restricted the growth of the tumor compared to adequate controls. The overall aim of the project is to validate the ability of our multi-omics/bioinformatics pipeline to identify and deliver neoantigens that can be used to suppress tumor growth.
2024-06-30 | E-MTAB-14130 | biostudies-arrayexpress
Project description:Whole Genome Sequencing of the murine breast cancer cell line 4T1 and of the murine melanoma cell line B16-ova was carried out with the aim of identifying somatic mutations. We also ran deep Mass Spectrometry proteomics analysis on the same cell lines, aiming to determine which somatic mutations carry over to the protein expression level. Further, we tested these cancer specific protein epitopes (putative neoantigens) for immunogenicity using mouse models. Finally, the putative neoantigens that showed good immunogenic potential were used in tumor growth control experiments with mice engrafted with the two tumor cell lines. In these experiments we tested whether cancer vaccines based on individual neoantigen peptides (MHC-I) restricted the growth of the tumor compared to adequate controls. The overall aim of the project is to validate the ability of our multi-omics/bioinformatics pipeline to identify and deliver neoantigens that can be used to suppress tumor growth. File names Sample names P10859_101_S1_L001_R1_001_BHKWV3CCXY 4T1_S1_L001_R1_001_BHKWV3CCXY P10859_101_S1_L001_R2_001_BHKWV3CCXY 4T1_S1_L001_R2_001_BHKWV3CCXY P10859_101_S1_L002_R1_001_BHKWV3CCXY 4T1_S1_L002_R1_001_BHKWV3CCXY P10859_101_S1_L002_R2_001_BHKWV3CCXY 4T1_S1_L002_R2_001_BHKWV3CCXY P10859_102_S2_L003_R1_001_BHKWV3CCXY B16-OVA_S2_L003_R1_001_BHKWV3CCXY P10859_102_S2_L003_R2_001_BHKWV3CCXY B16-OVA_S2_L003_R2_001_BHKWV3CCXY P10859_102_S2_L004_R1_001_BHKWV3CCXY B16-OVA_S2_L004_R1_001_BHKWV3CCXY P10859_102_S2_L004_R2_001_BHKWV3CCXY B16-OVA_S2_L004_R2_001_BHKWV3CCXY
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Project description:Treatment of cancer cells with anti-cancer drugs often fails to achieve complete remission. Yet, such drug treatments may induce alteration in the tumor’s gene expression patterns, including those of Cancer/Testis Antigens (CTA). The degradation products of such antigens can be presented as HLA peptides on the surface of the tumor cells and be developed into anti-cancer immunotherapeutics. For example, the DNA methyl transferase inhibitor, 5-aza-2'-deoxycytidine (Decitabine) has limited anti-tumor efficacy, yet it induces the expression of many genes, including CTAs that are normally silenced in the healthy adult tissues. In this study, the presentation of many new HLA peptides derived from CTAs and induced by Decitabine was demonstrated in three human Glioblastoma cell lines. Such presentation of CTA-derived HLA peptides can be exploited for development of new treatment modalities, combining drug treatment with anti-CTA targeted immunotherapy. The Decitabine-induced HLA peptidomes include many CTAs that are not normally detected in healthy tissues or in cancer cells, unless treated with the drug. In addition, the study included large-scale analyses of the simultaneous effects of Decitabine on the transcriptomes, proteomes and HLA peptidomes of the human Glioblastoma cells. It demonstrates the poor correlations between these three levels of gene expression, both in their total levels and in their response to the drug.
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