Table 2 Advantages, disadvantages and relevant cancers for each class of neoantigens
Neoantigen classification | Sources | Advantages | Disadvantages | Relevant cancer |
|---|---|---|---|---|
Genomic variants | Single-nucleotide variants (SNVs) | Simple prediction; relatively high burden | Similar to self-antigen; rarely shared between patients | Melanoma, glioblastoma, lung cancer (adeno and squamous), bladder cancer |
Insertions and deletion (INDEL) frameshift | More potential targets per mutation; more dissimilar from self-antigen; more immunogenic | Relatively low burden | MSI-H tumors, renal cell carcinomas (clear cell, papillary, and chromophobe) | |
Fusion genes | More dissimilar from self-antigen; shared targets between tumors; more potential targets per mutation; more immunogenic | Relatively low burden | Acute myelocytic leukemia, acute lymphocytic leukemia, chronic myeloid leukemia, sarcomas | |
Chromosomal rearrangements | High immunogenicity | Less well studied | Malignant pleural mesothelioma | |
Transcriptomic variants | RNA splicing | A large number of predicted targets; More dissimilar from self-antigen | Fewer tools available; not well validated in pre-clinical models; current tools do not account for nonsense mediated decay (NMD) | Acute myelocytic leukemia, chronic myelomonocytic leukemia, chronic lymphocytic leukemia, myelodysplastic syndrome |
Polyadenylation (pA) and RNA editing | Easy prediction | Less well studied | Chronic lymphocytic leukemia | |
Allegedly non-coding regions | Relatively high burden; more potential targets | Less well studied; fewer tools available | Acute lymphoblastic leukemias, lung cancers | |
Proteomic variants | Post-translational modifications (PTMs) | Shared between patients | Less well studied | leukemia, renal cancer, non-small cell lung cancer |
Proteasome processing | High specificity | Less well studied; fewer tools available | Acute myeloid leukemia | |
T cell epitopes associated with impaired peptide processing (TEIPP) | TEIPP-specific T cells can escape thymic selection | Less well studied; limited in HLA-I low or TAP-deficient tumors | Lung cancer | |
Viral-derived neoantigens | Viral open reading frames | High immunogenicity; more dissimilar from self-antigen; shared between patients; without apparent toxicity to normal tissues. | Limited in specific tumors | Hepatocellular carcinoma, Merkel cell carcinoma, nasopharyngeal carcinoma, head and neck cancer, cervical cancer, anal cancers |
