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

Terutsugu Koya; Kenichi Yoshida; Misa Togi; Yo Niida; Sumihito Togi; Hiroki Ura; Shuichi Mizuta; Tomohisa Kato Jr; Sohsuke Yamada; Takeo Shibata; Yi-Chang Liu; Shyng-Shiou Yuan; Deng-Chyang Wu; Hirohito Kobayashi; Taiju Utsugisawa; Hitoshi Kanno; Shigetaka Shimodaira

doi:10.3390/cancers15143627

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

Cancers (Basel). 2023 Jul 14;15(14):3627. doi: 10.3390/cancers15143627.

Authors

Terutsugu Koya^{1

2}, Kenichi Yoshida², Misa Togi^{1

2}, Yo Niida³, Sumihito Togi³, Hiroki Ura³, Shuichi Mizuta⁴, Tomohisa Kato Jr⁵, Sohsuke Yamada⁶, Takeo Shibata⁷, Yi-Chang Liu^{8

9}, Shyng-Shiou Yuan¹⁰, Deng-Chyang Wu¹¹, Hirohito Kobayashi¹², Taiju Utsugisawa¹³, Hitoshi Kanno¹³, Shigetaka Shimodaira^{1

2

5

13}

Affiliations

¹ Department of Regenerative Medicine, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan.
² Center for Regenerative Medicine, Kanazawa Medical University Hospital, Kahoku 920-0293, Ishikawa, Japan.
³ Division of Genomic Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan.
⁴ Department of Hematology and Immunology, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan.
⁵ Division of Stem Cell Medicine, Department of Advanced Medicine, Medical Research Institute, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan.
⁶ Department of Pathology and Laboratory Medicine, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan.
⁷ Department of Obstetrics and Gynecology, Kanazawa Medical University, Kahoku 920-0293, Ishikawa, Japan.
⁸ Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
⁹ Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
¹⁰ Office of Research & Development, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
¹¹ Internal Medicine, School of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
¹² Division of Transfusion and Cell Therapy, Tokyo Women's Medical University, Adachi Medical Center, Adachi 123-8558, Tokyo, Japan.
¹³ Department of Transfusion Medicine and Cell Processing, Tokyo Women's Medical University, Shinjuku 162-8666, Tokyo, Japan.

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.

Keywords: antigen-presenting cells; enzyme-linked immunosorbent assay; in silico prediction; memory T cells; personalized cancer vaccine.

Grants and funding

This work was supported by the ALP Institute for Regenerative Medicine Inc.; the Program on Open Innovation Platform with Enterprises, Research Institutes, and Academia of the JST under grant number JPMJOP1722; and JSPS KAKENHI under grant number JP22K07244.