Table 2.
Clinical development stage of neoantigen-targeted therapies.
| Alterations | Altered Molecule | Identification | Prediction | Most Advanced Development Stage | Example |
|---|---|---|---|---|---|
| SNV/indels | DNA | WES + RNA-seq | Available (many) | Phase 1/1b; several ongoing Phases 2/3 | Immunogenic responses observed in patients receiving peptide/DC/mRNA vaccines; or adoptive T cell therapy in different cancer types [147,148,149,170,171] |
| Gene fusion | DNA | WES + RNA-seq | Available (few) | Phase 2 | Immunogenic response but no clinical efficacy observed in patients with CML following bcr-abl peptide vaccination [172] |
| Alternative splicing | RNA | RNA-seq, Ribo-seq |
Available (few) | Preclinical | CD8 T cell recognition of the mutated splicing factor SF3B1 in patients with uveal melanoma [79] |
| Non-coding genomic regions | RNA | RNA-seq, Ribo-seq |
NA | Preclinical | Delayed tumor growth of CT26 tumors following cryptic peptide vaccination without proof of specific T cell response [92] |
| Transposable Elements | RNA | WES + RNA-seq, Ribo-seq |
Available (few) | Preclinical ongoing Phase 1 | Recognition of HERV antigens by CD8 T cells from patients [108,109] HERV-E TCR Transduced Autologous T Cells in Metastatic Kidney cancer patients (*) |
| Glycosylation | Protein | Mass spectrometry | NA | Phase 3 | No overall survival benefit with L-BLP25 peptide vaccine in NSCLC patients [129]; Improved progression free survival post TG4010 vaccine + chemotherapy in NSCLC patients [130] |
| Phosphorylation | Protein | Mass spectrometry | NA | Phase 1 | Some specific CD8 T cell responses were observed in melanoma patients who received pIRS2 and pBCAR3 peptide vaccines [133] |
| Citrullination | Protein | Mass spectrometry | NA | Preclinical | Delayed B16F1 tumor growth in HLA-DR4 transgenic mice following citrullinated peptide vaccination. Citrullinated-specific CD4 T cell responses also observed in PBMC from ovarian cancer patients [136] |
| Peptide splicing | Protein | Mass spectrometry | NA | Preclinical | Spliced peptide identified and recognized by CD8 T cells in renal cell carcinoma [137] or melanoma [138] patients, and from EBV-B cells [139] |
SNV: Single nucleotide variant; WES: Whole exome sequencing; seq: sequencing; NA: Not available. * ClinicalTrials.gov.