IDENTIFICATION OF MHC PEPTIDES USING MASS SPECTROMETRY FOR NEOANTIGEN DISCOVERY AND CANCER VACCINE DEVELOPMENT
Bibliographic record
Abstract
Immunotherapy with neoantigens presented by major histocompatibility complex (MHC) is one of the most promising approaches in cancer treatment. Using this approach, cancer vaccines can be designed to target tumor-specific mutations that are not found in normal tissues. Clinical trials have demonstrated an increased immune response and eradication of tumors after injecting synthetic peptides selected from the immunopeptidome. Although the sequence of MHC binding peptides can be predicted from genome sequencing and prediction algorithms, this approach results in large numbers of predicted peptides, requiring the confirmation by mass spectrometry (MS) analysis. Identification of MHC peptides by direct MS analysis of immunopeptidome is accurate and sensitive, with tens of thousands of unique peptides potentially identified from either cancer cell line or tumor tissue. Peptides with mutations can also be identified with patient-specific protein databases constructed from genome or transcriptome sequencing data. MS analysis also enables the characterization of the post-translational modifications (PTMs) of those antigens that cannot be predicted. Moreover, PTMs were found to be more efficient in triggering an immune response. In addition to reviewing recent advances in the identification of neoantigens using MS, the techniques for cancer vaccine candidate selection and formulation, vaccine delivery systems, and the potential for use in combination with other therapeutics are also discussed. It is anticipated that MS-based techniques will play an important role in future cancer vaccine development. © 2019 John Wiley & Sons Ltd. Mass Spec Rev 40:110-125, 2021.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.003 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".