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1.
Front Immunol ; 15: 1414737, 2024.
Article in English | MEDLINE | ID: mdl-38938562

ABSTRACT

This report details a case of pancreatic cancer with liver metastasis that exhibited a positive immune response to personalized immunization therapy. Our study involved the identification of neoantigens and their corresponding immunogenic peptides using an in-house bioinformatic pipeline. This process included the identification of somatic mutations through DNA/RNA sequencing of solid tumor tissue and blood liquid biopsy. Computational prediction techniques were then employed to identify novel epitopes, followed by the design and manufacture of patient-specific immunization peptides. In combination with standard-of-care chemotherapy, the patient received a sequence of 5 biweekly prime injections followed by 2 boost injections 2 and 5 months later. The peptides were emulsified in Montanide and the injection-site was conditioned with nivolumab and imiquimod. The combined regimen of peptide immunization and chemotherapy resulted in a notable decline in CA19-9 tumor marker levels following both prime and boost applications. Subsequent MRI assessments revealed a reduction in the size of liver metastases several months post-immunization initiation. Importantly, the patient showed and improved overall survival and reported an improved quality of life without experiencing significant treatment-related adverse effects. This case underscores the potential benefits of personalized peptide-based immunization as an adjunctive therapy in the treatment of advanced pancreatic cancer, showcasing promising outcomes in tumor marker reduction, tumor shrinkage, and enhanced patient well-being.


Subject(s)
Antigens, Neoplasm , Pancreatic Neoplasms , Precision Medicine , Humans , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/immunology , Pancreatic Neoplasms/pathology , Antigens, Neoplasm/immunology , Liquid Biopsy/methods , Cancer Vaccines/immunology , Cancer Vaccines/administration & dosage , Cancer Vaccines/therapeutic use , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Liver Neoplasms/immunology , Male , Peptides/immunology , Peptides/administration & dosage , Middle Aged , Vaccines, Subunit/administration & dosage , Immunization , Female , Biomarkers, Tumor
2.
Vaccines (Basel) ; 11(6)2023 May 25.
Article in English | MEDLINE | ID: mdl-37376412

ABSTRACT

Cancer neoantigens that arise from somatic mutations have emerged as important targets for personalized immunization. Here, we report an improved overall survival of a HER2-positive metastatic breast cancer patient using a bioinformatic-based personalized peptide immunization called BITAP (BioInformatic Tumor Address Peptides). The epitopes were predicted using our in-house bioinformatic pipeline, and the immunogenicity was tested by IFN-γ ELISPOT and intracellular cytokine staining assays. In total, a significant peptide-specific T-cell response was detected against 18 out of the 76 (≈24%) tested peptides. The patient's follow-up by measuring serologic markers showed a significant reduction in the tumor marker levels following BITAP immunization. Along with standard treatment, the patient treated with the BITAP showed stable disease with a remarkably improved overall survival, and no serious treatment-related adverse effects. In conclusion, our findings suggest that BITAP immunization is feasible, and safe, and may induce tumor regressions in patients with HER2-positive subsets of breast cancer.

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