1. WT1 epitope-specific IgG and IgM antibodies for immune-monitoring in patients with advanced sarcoma treated with a WT1 peptide cancer vaccine.
- Author
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Alzaaqi, Shouq, Naka, Norifumi, Hamada, Kenichiro, Hosen, Naoki, Kanegae, Mizuki, Outani, Hidetatsu, Adachi, Mayuko, Imanishi, Rin, Morii, Eiichi, Iwai, Miki, Nakata, Jun, Fujiki, Fumihiro, Morimoto, Soyoko, Nakajima, Hiroko, Nishida, Sumiyuki, Tsuboi, Akihiro, Oka, Yoshihiro, Sugiyama, Haruo, and Oji, Yusuke
- Subjects
PEPTIDES ,CANCER vaccines ,ANTIGENS ,MONONUCLEAR leukocytes ,IMMUNOGLOBULIN G ,IMMUNOGLOBULINS - Abstract
The Wilms' tumor gene WT1 is highly expressed in various malignancies and may be a common target antigen for cancer immunotherapy. In our group, peptide-based cancer vaccines targeting WT1 CTL epitopes were developed as an immunotherapy for these malignancies. In the present study, WT1 epitope-specific immune responses were analyzed in 31 patients with advanced sarcoma with human leukocyte antigen-A*24:02- and WT1-expressing tumors who received the WT1-235 peptide vaccine as monotherapy. The serum levels of IgG and IgM antibodies against the target epitope WT1-235 and the non-target epitopes WT1-332 and WT1-271 were measured using ELISA. IgM antibodies against WT1-235, WT1-332 and WT1-271 were detected in three (9.6%), four (12.9%) and 20 patients (64.5%), respectively, prior to vaccine administration, indicating immune recognition of the WT1 antigen prior to administering the vaccine. Of 15 patients who had completed the 3-month treatment protocol, WT1-235 IgG was positive in five (33.3%) patients. An enzyme-linked immunospot assay revealed that WT1-235 epitope-specific IL-10 production/secretion in peripheral blood mononuclear cells declined in the first month of vaccine administration in all three patients with positivity for WT1-235 IgM at the start of the vaccine. Furthermore, positivity for both WT1-235 and WT1-271 IgM antibodies at the start of treatment was associated with unfavorable tumor control at 3 months after vaccine administration. These results suggested that WT1 epitope-specific IgG and IgM antibodies may be utilized as immune-monitoring markers for WT1 peptide cancer vaccine immunotherapy. The trials were entered in the University hospital Medical Information Network (UMIN) Clinical Trials Registry (https://www.umin.ac.jp/ctr ; no. UMIN000002001 on May 24, 2009 and no. UMIN000015997 on December 20, 2014). [ABSTRACT FROM AUTHOR]
- Published
- 2022
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