Takashi Morisaki1, Takafumi Morisaki2,3, Makoto Kubo3, Hideya Onishi4, Tatsuya Hirano5, Shinji Morisaki2,4,6, Masatoshi Eto7, Keisuke Monji7, Ario Takeuchi7, Shinichiro Nakagawa2, Hiroto Tanaka2, Norihiro Koya2, Masayo Umebayashi2, Kenta Tsujimura2, Poh Yin Yew8, Sachiko Yoshimura8, Kazuma Kiyotani9, Yusuke Nakamura9. 1. Fukuoka General Cancer Clinic, Fukuoka, Japan tmorisaki@cancer-clinic.jp. 2. Fukuoka General Cancer Clinic, Fukuoka, Japan. 3. Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 4. Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 5. Department of Surgery, Sada Hospital, Fukuoka, Japan. 6. Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 7. Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. 8. Cancer Precision Medicine Inc., Kawasaki, Japan. 9. Cancer Precision Medicine Center, Japanese Foundation for Cancer Research, Tokyo, Japan.
Abstract
BACKGROUND/AIM: Neoantigens are tumor-specific antigens that emerge due to gene mutations in tumor cells, and are highly antigenic epitopes that escape central immune tolerance in the thymus, making cancer vaccine therapy a desirable option. PATIENTS AND METHODS: Tumor neoantigens were predicted in 17 patients with advanced cancer. They were resistant to the standard treatment regime, and their synthetic peptides were pulsed to the patient's monocyte-derived dendritic cells (DCs), and administered to the patient's lymph nodes via ultrasound. RESULTS: Some patients showed sustained tumor shrinkage after this treatment, while some did not respond, showing no ELISpot reaction. Although the number of mutations and the predicted neoantigen epitopes differed between patients, the clinical effect depended more on the presence or absence of an immune response after vaccination rather than the number of neoantigens. CONCLUSION: Intranodal neoantigen peptide-pulsed DC vaccine administration therapy has clinical and immunological efficacy and safety.
BACKGROUND/AIM: Neoantigens are tumor-specific antigens that emerge due to gene mutations in tumor cells, and are highly antigenic epitopes that escape central immune tolerance in the thymus, making cancer vaccine therapy a desirable option. PATIENTS AND METHODS: Tumor neoantigens were predicted in 17 patients with advanced cancer. They were resistant to the standard treatment regime, and their synthetic peptides were pulsed to the patient's monocyte-derived dendritic cells (DCs), and administered to the patient's lymph nodes via ultrasound. RESULTS: Some patients showed sustained tumor shrinkage after this treatment, while some did not respond, showing no ELISpot reaction. Although the number of mutations and the predicted neoantigen epitopes differed between patients, the clinical effect depended more on the presence or absence of an immune response after vaccination rather than the number of neoantigens. CONCLUSION: Intranodal neoantigen peptide-pulsed DC vaccine administration therapy has clinical and immunological efficacy and safety.
Authors: Lorna Leal; Elvira Couto; Sonsoles Sánchez-Palomino; Núria Climent; Irene Fernández; Laia Miralles; Yolanda Romero; Tania González; Maria José Maleno; Blanca Paño; Judit Pich; Carlos Nicolau; José Maria Gatell; Montserrat Plana; Felipe García Journal: Front Immunol Date: 2021-11-11 Impact factor: 7.561