| Summary: | 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 × 10<sup>7</sup> 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 KRAS<sup>WT</sup>, HLA-DRB1*09:01-compliant KRAS<sup>WT or G12D</sup>, or HLA-A*31:01-matched SMAD4<sup>WT</sup>, and HLA-DRB1*04:01-matched SMAD4<sup>G365D</sup> peptides in two completed cases, respectively. Moreover, SMAD4<sup>WT</sup>-specific CD8<sup>+</sup> 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.
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