Retrospective Analysis of HLA Class II-Restricted Neoantigen Peptide-Pulsed Dendritic Cell Vaccine for Breast Cancer.

Simple Summary: Cancer vaccines targeting neoantigens represent a new modality for cancer treatment. We used a neoantigen prediction pipeline involving a combination of whole genome and RNA sequencing and in silico analyses to predict neoantigens and pulsed patient-derived dendritic cells with the synthesized HLA class II peptides. We administered this vaccine (Neo-P DC vaccine) to five breast cancer patients post-surgery to evaluate the immune response against the Neo-P Dc vaccine. We confirmed a lymphocyte response particularly for HLA class II-restricted neoantigens containing HLA class I epitopes in all cases. No relapses have been reported. These results indicate the immunological efficacy of the HLA class II-restricted neoantigen peptide dendritic cell vaccine against breast cancer. Background/Objectives: Neoantigens have attracted attention as ideal therapeutic targets for anti-tumour immunotherapy because the T cells that respond to neoantigens are not affected by central immune tolerance. Recent findings have revealed that the activation of CD4-positive T cells plays a central role in antitumor immunity, and thus targeting human leukocyte antigen (HLA) class II-restricted neoantigens, which are targets of CD4-positive T cells, is of significance. However, there are very few detailed reports of neoantigen vaccine therapies that use an HLA class II-restricted long peptide. In the present study, we retrospectively analysed the ability of HLA class II-restricted neoantigen-pulsed dendritic cell vaccines to induce immune response in five breast cancer patients. Methods: We performed whole exome and RNA sequencing of breast cancer tissues and neoantigen prediction using an in silico pipeline. We then administered dendritic cells pulsed with synthesized an HLA class II-restricted long peptide containing an epitope with high affinity to HLA class I in the lymph node. Results: ELISPOT analysis confirmed that a T-cell response specific for the HLA class II-restricted neoantigen was induced in all cases. TCR repertoire analysis of peripheral blood mononuclear cells before and after treatment in three patients showed increases of specific T-cell clones in two of the three patients. Importantly, no recurrence was observed in all patients. Conclusions: Our analysis demonstrated the immunological efficacy of the HLA class II-restricted neoantigen peptide dendritic cell vaccine against breast cancer and provides useful information for the development of neoantigen vaccine therapy for breast cancer. [ABSTRACT FROM AUTHOR]