Clinical Trial on the Safety and Tolerability of Personalized Cancer Vaccines Using Human Platelet Lysate-Induced Antigen-Presenting Cells.
Terutsugu KoyaKenichi YoshidaMisa TogiYo NiidaSumihito TogiHiroki UraShuichi MizutaTomohisa KatoSohsuke YamadaTakeo ShibataYi-Chang LiuShyng-Shiou F YuanDeng-Chyang WuHirohito KobayashiTaiju UtsugisawaHitoshi KannoShigetaka ShimodairaPublished in: Cancers (2023)
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 7 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 WT , HLA-DRB1*09:01-compliant KRAS WT or G12D , or HLA-A*31:01-matched SMAD4 WT , and HLA-DRB1*04:01-matched SMAD4 G365D peptides in two completed cases, respectively. Moreover, SMAD4 WT -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.
Keyphrases
- clinical trial
- immune response
- papillary thyroid
- phase ii
- squamous cell
- open label
- endothelial cells
- induced apoptosis
- dendritic cells
- epithelial mesenchymal transition
- newly diagnosed
- squamous cell carcinoma
- lymph node metastasis
- study protocol
- ejection fraction
- stem cells
- double blind
- signaling pathway
- endoplasmic reticulum stress
- dna methylation
- patient reported outcomes
- inflammatory response
- patient reported
- genome wide
- single cell