Sensitive neoantigen discovery by real-time mutanome-guided immunopeptidomics

Area of Science:

• Immunology
• Oncology
• Analytical Chemistry

Background:

• Targeting cancer-specific HLA-peptide complexes is crucial for effective cancer immunotherapy.
• Mutated neoantigens offer high immunogenicity and cancer-specificity for therapeutic targeting.
• Mass spectrometry (MS)-based immunopeptidomics is vital for identifying naturally presented immunogenic targets.

Purpose of the Study:

• To present NeoDiscMS, an advanced system for personalized immunopeptidomics data acquisition.
• To enhance the sensitivity and global depth of immunopeptidome analysis for clinical applications.
• To improve the accuracy and confidence of neoantigen identification in cancer patients.

Main Methods:

• NeoDiscMS utilizes next-generation sequencing-guided real-time spectral acquisitions for data acquisition.
• The method is designed for ease of implementation, catering to scarce sample inputs and short turnaround times.
• It extends the capabilities of the NeoDisc platform for personalized immunopeptidomics.

Main Results:

• NeoDiscMS maximizes analytical sensitivity while minimizing the loss of global immunopeptidome depth.
• Detection of peptides from tumor-associated antigens is enhanced by up to 20%.
• NeoDiscMS provides improved confidence in neoantigen identification compared to existing gold-standard methods.

Conclusions:

• NeoDiscMS represents a significant advancement in personalized clinical antigen discovery.
• The system facilitates more confident neoantigen detection, crucial for developing targeted immunotherapies.
• Its ease of implementation makes it suitable for routine clinical use in cancer research.