부산대학교 도서관

Simple Summary: In this study, we developed human platelet lysate-induced antigen-presenting cells (HPL-APCs) from peripheral monocytes with a high potency of presentation ability. This study aimed to verify the safety, tolerability, and immunoinducibility of HPL-APCs loaded with cancer candidate antigens as a Phase I study. As a result of the interim analysis, safety and tolerability were confirmed in three enrolled patients, and the immune response to cancer antigen candidate peptides predicted in silico was confirmed in two completed cases. This clinical study is the first to verify the feasibility and immunoinducibility of a personalized cancer vaccine using HPL-APCs that would be expected to demonstrate further antitumor activity through optimized combination therapies. Research and development of personalized cancer vaccines as precision medicine are ongoing. We predicted human leukocyte antigen (HLA)-compatible cancer antigen candidate peptides based on patient-specific cancer genomic profiles and performed a Phase I clinical trial for the safety and tolerability of cancer vaccines with human platelet lysate-induced antigen-presenting cells (HPL-APCs) from peripheral monocytes. Among the five enrolled patients, two patients completed six doses per course (2–3 × 107 cells per dose), and an interim analysis was performed based on the immune response. An immune response was detected by enzyme-linked immunosorbent spot (ELISpot) assays to HLA-A*33:03-matched KRASWT, HLA-DRB1*09:01-compliant KRASWT or G12D, or HLA-A*31:01-matched SMAD4WT, and HLA-DRB1*04:01-matched SMAD4G365D peptides in two completed cases, respectively. Moreover, SMAD4WT-specific CD8+ effector memory T cells were amplified. However, an attenuation of the acquired immune response was observed 6 months after one course of cancer vaccination as the disease progressed. This study confirmed the safety and tolerability of HPL-APCs in advanced and recurrent cancers refractory to standard therapy and is the first clinical report to demonstrate the immunoinducibility of personalized cancer vaccines using HPL-APCs. Phase II clinical trials to determine immune responses with optimized adjuvant drugs and continued administration are expected to demonstrate efficacy. [ABSTRACT FROM AUTHOR]