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Learn MoreAntigen development has accelerated the development of tumor immunotherapies, such as cancer vaccines, adoptive cell therapy, and antibody therapies. Based on next-generation sequencing and bioinformatics technologies, Alfa Cytology helps customers develop cancer antigens and understand their mechanisms of inducing anti-tumor immune responses.
Tumor-specific antigens (TSA) are antigens produced by tumor cells as a result of various tumor-specific alterations, such as genomic mutations, dysregulated RNA splicing, disrupted post-translational modifications, and integrative viral open reading frames. Tumor-associated antigens (TAA) are molecules that are overexpressed or aberrantly expressed in tumor cells or tumor-related processes. Highly immunogenic TSAs provide superior targets for personalized cancer immunotherapy compared to TAAs and may serve as prospective predictors of tumor survival prognosis and immune checkpoint blockade response.
Fig.1 Overview of the tumor antigen production. (Xie, N., et al., 2023)
Tumor antigen discovery provides the molecular basis for tumor immunotherapy, in particular tumor antibody therapies. However, given the wide variations in tumor types, tumor lesions, and patients, precision immunotherapy requires the detection and prediction of tumor specific antigen candidates based on different characteristics of patients and tumors.
Alfa Cytology has extensive experience in oncology research and can provide tumor antigen discovery services to our clients. We mainly have two strategies for identifying neoantigens. The immunogenomic approach creates virtual peptidomes via an in silico NGS-based approach, while the immunopeptidome strategy uses MS to analyze MHC-loaded peptides.
Genome-based Tumor Antigen Discovery
Alfa Cytology provides data to support tumor antigen development using methods such as NGS, RNA-seq, and full-length transcriptome sequencing. Whole-exome sequencing (WES) data from tumor and normal DNA is used to map tumor-specific genetic abnormalities. RNA-seq can be used to detect alternative splicing events and estimate the relative frequency of expression of mutant alleles. Full-length transcriptome sequencing provides complementary information to RNA-seq to determine allele-specific transcription and splicing.
Immunopeptidome-based Tumor Antigen Discovery
Alfa Cytology uses immunopeptidome technology to identify peptides attached to major histocompatibility (MHC) in a high-throughput manner to predict tumor neoantigens. In addition to validating neoantigens arising from abnormalities in DNA sequence or RNA expression, mass spectrometry (MS) based proteomics provides the "gold standard" for neoantigen detection at the protein level. In addition, MS can be combined with NGS to further detect TSA generated by somatic mutations, non-coding RNA, and proteasome splicing.
Immunogenic tumor specific antigen candidates must meet two requirements, including the need to assess appropriate MHC molecular presentation and effective TCR recognition. Alfa Cytology helps predict tumor antigen-specific T cell recognition through in silico techniques. To assess the possible application of tumor antigen candidates more accurately in immunotherapy, Alfa Cytology provides experimental validation of their T cell reactivity, including T cell-based assays, multi-color labeled MHC tetramers, enzyme-linked immunosorbent spot (ELISpot) and T cell profiling, and so on.
Antigen Prediction
Computational prediction or experimental screening to identify potential antigens.
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Antigen Identification
Identification of target antigens based on specific requirements or desired immune response.
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Antigen Synthesis
Chemical or biological synthesis of the designed antigens.
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Characterization
Comprehensive characterization of antigens, including structural analysis and functional validation.
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Evaluation
Evaluation of antigen's ability to induce an immune response through in vitro or in vivo assays.
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Tumor specific antigens play a key role in cancer immunotherapies, including cancer vaccines, ACT, antibody-based therapies, and immune checkpoint blockades (ICB). Alfa Cytology offers antigen development services, which provide validated targets for the development of new therapies. Please contact us for more information.
Reference
For research use only.