Akihisa Sawada1, Masami Inoue1, Osamu Kondo1, Kayo Yamada-Nakata1, Takashi Ishihara1, Yuko Kuwae2,3, Masanori Nishikawa4, Yasuhiro Ammori5, Akihiro Tsuboi6, Yusuke Oji7, Maho Koyama-Sato1, Yoshihiro Oka8,9,10, Masahiro Yasui1, Haruo Sugiyama11, Keisei Kawa1. 1. Department of Hematology/Oncology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan. 2. Department of Pathology and Clinical Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan. 3. Department of Diagnostic Pathology, Graduate School of Medicine, Osaka City University, Osaka, Japan. 4. Department of Radiology, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan. 5. Pharmacy, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka, Japan. 6. Department of Cancer Immunotherapy, Osaka University Graduate School of Medicine, Osaka, Japan. 7. Department of Cancer Stem Cell Biology, Osaka University Graduate School of Medicine, Osaka, Japan. 8. Department of Cancer Immunology, Osaka University Graduate School of Medicine, Osaka, Japan. 9. Department of Respiratory Medicine, Allergy and Rheumatic Diseases, Osaka University Graduate School of Medicine, Osaka, Japan. 10. Department of Immunopathology, WPI Immunology Frontier Research Center, Osaka University, Osaka, Japan. 11. Department of Functional Diagnostic Science, Osaka University Graduate School of Medicine, Osaka, Japan.
Abstract
BACKGROUND: Advances in cancer immunotherapy in the pediatric field are needed in order to improve the prognosis of children with malignancies. We conducted a prospective phase I/II study of WT1 peptide vaccination for children with relapsed or refractory malignancies. METHODS: The main eligibility criteria were affected tissues or leukemic cells expressing the WT1 gene, and patients (and donors for allogeneic hematopoietic stem cell transplantation) having HLA-A*24:02. Vaccination using the WT1 peptide (CYTWNQMNL), which was modified for higher affinity to this HLA-type molecule with the adjuvant Montanide ISA51, was performed weekly 12 times. RESULTS: Twenty-six patients were enrolled and 13 (50.0%) completed the vaccination 12 times. Evidence for the induction of WT1-specific cytotoxic T-lymphocyte (CTL) responses without severe systemic side effects was obtained. Two out of 12 patients with bulky disease exhibited a transient clinical effect (one mixed response and one stable disease), three out of six patients with minimal residual disease achieved transient molecular remission, and five out of eight patients without a detectable level of the molecular marker, but with a high risk of relapse, had the best outcome of long-term continuous complete remission. CONCLUSIONS: WT1 vaccination is a safe immunotherapy and induced WT1-specific CTL responses in children; however, as a single agent, vaccination only provided patients in remission, but with a high risk of relapse, with "long-term benefits" in the context of its use for relapse prevention. WT1 peptide-based treatments in combination with other modalities, such as anti-tumor drugs or immunomodulating agents, need to be planned.
BACKGROUND: Advances in cancer immunotherapy in the pediatric field are needed in order to improve the prognosis of children with malignancies. We conducted a prospective phase I/II study of WT1 peptide vaccination for children with relapsed or refractory malignancies. METHODS: The main eligibility criteria were affected tissues or leukemic cells expressing the WT1 gene, and patients (and donors for allogeneic hematopoietic stem cell transplantation) having HLA-A*24:02. Vaccination using the WT1 peptide (CYTWNQMNL), which was modified for higher affinity to this HLA-type molecule with the adjuvant MontanideISA51, was performed weekly 12 times. RESULTS: Twenty-six patients were enrolled and 13 (50.0%) completed the vaccination 12 times. Evidence for the induction of WT1-specific cytotoxic T-lymphocyte (CTL) responses without severe systemic side effects was obtained. Two out of 12 patients with bulky disease exhibited a transient clinical effect (one mixed response and one stable disease), three out of six patients with minimal residual disease achieved transient molecular remission, and five out of eight patients without a detectable level of the molecular marker, but with a high risk of relapse, had the best outcome of long-term continuous complete remission. CONCLUSIONS:WT1 vaccination is a safe immunotherapy and induced WT1-specific CTL responses in children; however, as a single agent, vaccination only provided patients in remission, but with a high risk of relapse, with "long-term benefits" in the context of its use for relapse prevention. WT1 peptide-based treatments in combination with other modalities, such as anti-tumor drugs or immunomodulating agents, need to be planned.
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Authors: Sévérine de Bruijn; Sébastien Anguille; Joris Verlooy; Evelien L Smits; Viggo F van Tendeloo; Maxime de Laere; Koenraad Norga; Zwi N Berneman; Eva Lion Journal: Cancers (Basel) Date: 2019-09-19 Impact factor: 6.639