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Clinical Trial on the Safety and Tolerability of Personalized Cancer Vaccines Using Human Platelet Lysate-Induced Antigen-Presenting Cells.

ABSTRACT: 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 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.

SUBMITTER: Koya T

PROVIDER: S-EPMC10377585 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Clinical Trial on the Safety and Tolerability of Personalized Cancer Vaccines Using Human Platelet Lysate-Induced Antigen-Presenting Cells.

Koya Terutsugu T Yoshida Kenichi K Togi Misa M Niida Yo Y Togi Sumihito S Ura Hiroki H Mizuta Shuichi S Kato Tomohisa T Yamada Sohsuke S Shibata Takeo T Liu Yi-Chang YC Yuan Shyng-Shiou SS Wu Deng-Chyang DC Kobayashi Hirohito H Utsugisawa Taiju T Kanno Hitoshi H Shimodaira Shigetaka S

Cancers 20230714 14

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 ...[more]

PMID: 37509288

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Project description:Platelet recovery is delayed after umbilical cord blood transplant (UCBT). Romiplostim is a thrombopoietin receptor agonist that has the potential to improve platelet engraftment after UCBT. The purpose of this study was to determine the safety profile and maximum tolerated dose (MTD) of romiplostim and to investigate whether romiplostim accelerates platelet recovery post-UCBT. It was a single-center, dose-finding, safety and tolerability phase I trial of weekly romiplostim in 20 adult patients who failed to achieve an un-transfused platelet count of 20 × 109/L by day +28 post-UCBT. Romiplostim was administered at the assigned dose as 6 weekly injections beginning by day +42 post-UCBT. Four dose levels (4, 6, 8, and 10 µg/kg per dose) were evaluated. The MTD of romiplostim was determined by the continual reassessment method, with a goal to identify a dose level with desired toxicity rate of ≤20%. Median age of the patients was 59.5 years, and 60% were female. Eleven patients received nonmyeloablative (NMA) double UCBT, seven patients received myeloablative single UCBT, and two patients received NMA single UCBT. Two patients received 4 µg/kg per dose, two received 6 µg/kg per dose, four received 8 µg/kg per dose, and the remaining 12 received 10 µg/kg per dose. Only five patients completed the full six doses of treatment. Of the 15 patients who received fewer than six doses, 12 were due to a platelet count of >100 × 109/L, two were due to platelet count of >400 × 109/L, and one was due to right upper extremity edema without thrombosis. All romiplostim-treated patients achieved platelet engraftment to 20 × 109/L at a median of 45 days post-UCBT compared to 90% of controls at a median of 45 days (P = .08). Similarly, 90% of romiplostim-treated patients achieved platelet engraftment to 50 × 109/L at a median of 48 days compared to 75% of controls at a median of 52 days (P = .09). All dose levels were effective with low toxicity; therefore, the MTD of romiplostim was 10 µg/kg per dose, and romiplostim is a safe and potentially effective therapy to counter delayed platelet recovery post-UCBT.

Dataset Information

Clinical Trial on the Safety and Tolerability of Personalized Cancer Vaccines Using Human Platelet Lysate-Induced Antigen-Presenting Cells.

Publications

Clinical Trial on the Safety and Tolerability of Personalized Cancer Vaccines Using Human Platelet Lysate-Induced Antigen-Presenting Cells.

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