Neoantigen identification strategies enable personalized immunotherapy in refractory solid tumors

Area of Science:

• Oncology
• Immunology
• Bioinformatics

Background:

• Genomic and bioinformatic advances enable dissection of immune responses to personalized neoantigens.
• Timely and efficient neoantigen identification remains a challenge for personalized cancer immunotherapy.

Purpose of the Study:

• To establish and evaluate feasible pipelines for neoantigen identification.
• To generate personalized neoantigen vaccines and T cells for cancer immunotherapy.

Main Methods:

• Developed two neoantigen identification pipelines: de novo synthesis of high-affinity mutant peptides and matching patient mutations to a shared neoantigen library.
• Identified candidate neoepitopes by assessing memory T-cell recall responses in vitro.
• Generated neoantigen-loaded dendritic cell vaccines and neoantigen-reactive T cells for immunotherapy.

Main Results:

• Immunogenic neo-epitopes were recognized by autologous T cells in 3/4 (de novo synthesis) and 6/13 (shared library) patients.
• One patient with metastatic thymoma achieved a complete and durable response (>29 months).
• One patient with metastatic pancreatic cancer showed an immune-related partial response; others had prolonged disease stabilization (median PFS 8.6 months).

Conclusions:

• The study provides feasible pipelines for neoantigen identification.
• Tailoring neoantigens through these strategies can advance translational immunotherapy research.