1. Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide
- Author
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Mayuko Adachi, Miki Iwai, Naoki Hosen, Satoshi Morita, Junichi Sakamoto, Yusuke Oji, Yoshihiro Oka, Yoshiki Nakae, Naoya Hashimoto, Toshiki Yoshimine, Hiroko Nakajima, Yui Murakami, Fumihiro Fujiki, Masahiro Iwamoto, Yasuyoshi Chiba, Manabu Kawakami, Ryo Ichinohasama, Sumiyuki Nishida, Akihiro Tsuboi, Soyoko Morimoto, Olga A. Elisseeva, Satoshi Takashima, Shuichi Izumoto, Jun Nakata, Naoki Kagawa, and Haruo Sugiyama
- Subjects
Male ,0301 basic medicine ,Cancer Research ,HLA-A24 Antigen ,Peptide ,urologic and male genital diseases ,Subclass ,0302 clinical medicine ,Cytotoxic T cell ,chemistry.chemical_classification ,Predictive marker ,biology ,Vaccination ,Middle Aged ,Prognosis ,Combined Modality Therapy ,female genital diseases and pregnancy complications ,Leukemia ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Female ,Immunotherapy ,Antibody ,predictive marker ,Adult ,congenital, hereditary, and neonatal diseases and abnormalities ,WT1 peptide‐based immunotherapy ,Enzyme-Linked Immunosorbent Assay ,Tumor Immunology and Microenvironment ,WT1 IgG antibody ,Cancer Vaccines ,Young Adult ,03 medical and health sciences ,Immune system ,Cell Line, Tumor ,medicine ,Humans ,WT1 Proteins ,Aged ,urogenital system ,business.industry ,fungi ,glioblastoma ,Th1 Cells ,medicine.disease ,030104 developmental biology ,chemistry ,Immunoglobulin G ,Immunology ,biology.protein ,Cancer research ,Peptides ,business ,Biomarkers ,T-Lymphocytes, Cytotoxic - Abstract
We previously evaluated Wilms’ tumor gene 1 (WT1) peptide vaccination in a large number of patients with leukemia or solid tumors and have reported that HLA‐A*24:02 restricted, 9‐mer WT1‐235 peptide (CYTWNQMNL) vaccine induces cellular immune responses and elicits WT1‐235‐specific cytotoxic T lymphocytes (CTLs). However, whether this vaccine induces humoral immune responses to produce WT1 antibody remains unknown. Thus, we measured IgG antibody levels against the WT1‐235 peptide (WT1‐235 IgG antibody) in patients with glioblastoma multiforme (GBM) receiving the WT1 peptide vaccine. The WT1‐235 IgG antibody, which was undetectable before vaccination, became detectable in 30 (50.8%) of a total of 59 patients during 3 months of WT1 peptide vaccination. The dominant WT1‐235 IgG antibody subclass was Th1‐type, IgG1 and IgG3. WT1‐235 IgG antibody production was significantly and positively correlated with both progression‐free survival (PFS) and overall survival (OS). Importantly, the combination of WT1‐235 IgG antibody production and positive delayed type‐hypersensitivity (DTH) to the WT1‐235 peptide was a better prognostic marker for long‐term OS than either parameter alone. These results suggested that WT1‐235 peptide vaccination induces not only WT1‐235‐specific CTLs as previously described but also WT1‐235‐specific humoral immune responses associated with antitumor cellular immune response. Our results indicate that the WT1 IgG antibody against the WT1 peptide may be a useful predictive marker, with better predictive performance in combination with DTH to WT1 peptide, and provide a new insight into the antitumor immune response induction in WT1 peptide vaccine‐treated patients., What's new? The Wilms' tumor gene 1 (WT1) antigen is a promising target for immunotherapeutic strategies against glioblastoma multiforme (GBM), a brain tumor with poor survival rates. The present study shows that vaccination with WT1‐235 peptide can induce WT1‐235‐specific humoral immune responses in GBM patients. WT1‐235 IgG antibody production was significantly associated with prolonged progression‐free survival and overall survival. Survival times were significantly longer in GBM patients with positive delayed‐type hypersensitivity (DTH) responses to WT1 peptide. Thus, in WT1 vaccine‐treated GBM patients, especially those exhibiting positive DTH responses, WT1‐235 IgG antibody production can predict long‐term survival.
- Published
- 2016