WT1 Peptide‐Based Immunotherapy for Patients with Lung Cancer: Report of Two Cases

Tsuboi, Akihiro; Oka, Y.; Osaki, Tadashi; Kumagai, Toru; Tachibana, Isao; Hayashi, Seiji; Murakami, Masaki; Nakajima, Hiroyuki; Elisseeva, Olga A.; Wu, Fei; Masuda, Takayuki; Yasukawa, Masaki; Oji, Yusuke; Kawakami, Manabu; Hosen, Naoki; Ikegame, Kazuhiro; Yoshihara, Satoshi; Udaka, Keiko; Nakatsuka, Shin‐ichi; Aozasa, Katsuyuki; Kawase, Ichiro; Sugiyama, Haruo

doi:10.1111/j.1348-0421.2004.tb03503.x

Cited by 64 publications

(71 citation statements)

References 31 publications

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“…Clinical trials of WT1 peptide-based cancer immunotherapy showed that WT1 vaccination induced a reduction in tumor size or decrease in tumor marker levels in breast cancer, lung cancer, and leukemia. 28,29 The results of the present study provide a rationale for immunotherapy targeting WT1 as a new treatment strategy for various kinds of tumors resistant to conventional surgery or chemoradiotherapy.…”

Section: Figurementioning

confidence: 84%

“…The clinical trial of a WT1 peptide-based cancer immunotherapy is on-going: WT1 vaccination was safe in all cases and clearly effective against several kinds of malignancies. 28,29 In routine practice, immunohistochemical analysis for WT1 expression using routinely processed histologic sections is essential to judge the eligibility of a patient for this immunotherapy. The present study was conducted to examine the availability of the immunohistochemical detection of WT1 in various human cancer cells with the use of a polyclonal and/or monoclonal antibody.…”

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confidence: 99%

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Immunohistochemical detection of WT1 protein in a variety of cancer cells

et al. 2006

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WT1 was first identified as a tumor suppressor involved in the development of Wilms' tumor. Recently, oncogenic properties of WT1 have been demonstrated in various hematological malignancies and solid tumors. Because WT1 has been identified as a molecular target for cancer immunotherapy, immunohistochemical detection of WT1 in tumor cells has become an essential part of routine practice. In the present study, the expression of WT1 was examined in 494 cases of human cancers, including tumors of the gastrointestinal and pancreatobiliary system, urinary tract, male and female genital organs, breast, lung, brain, skin, soft tissues and bone by immunohistochemistry using polyclonal (C-19) and monoclonal (6F-H2) antibodies against WT1 protein. Staining for C-19 and 6F-H2 was found in 35-100 and 5-88% of the cases of each kind of tumor, respectively. WT1-positive tumors included tumor of the stomach, prostate, and biliary and urinary systems, and malignant melanomas. A majority of the positive cases showed diffuse or granular staining in the cytoplasm, whereas ovarian tumors and desmoplastic small round cell tumors frequently showed nuclear staining. Glioblastomas, some of soft tissue sarcomas, osteosarcomas, and malignant melanomas of the skin showed extremely strong cytoplasmic staining as compared with other tumors. Western blot analysis showed that WT1 protein was predominantly expressed in the cytoplasm of the tumor cells in two cases of lung adenocarcinoma, supporting the intracytoplasmic staining for WT1 using immunohistochemistry. Immunohistochemical detection with routinely processed histologic sections could provide meaningful information on the expression of WT1 in cancer cells.

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Section: Figurementioning

confidence: 84%

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confidence: 99%

Immunohistochemical detection of WT1 protein in a variety of cancer cells

et al. 2006

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“…From the 114 studies, full-text was unavailable for one study 13 , 2 studies were duplicates published under different titles 14,15 , one study only described the study design 16 and 6 studies did not report safety, tolerability and/or toxicity results 7,[17][18][19][20][21] . These together with 11 case reports [22][23][24][25][26][27][28][29][30][31][32] and 2 letters to the editor were excluded 33,34 . Ultimately, a total of 91 studies were included in the systemic safety review.…”

Section: Resultsmentioning

confidence: 99%

Safety and tolerability evaluation of the use of Montanide ISA™51 as vaccine adjuvant: A systematic review

Doorn¹,

Liu²,

Huckriede³

et al. 2015

Human Vaccines & Immunotherapeutics

105

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“…Indeed, a previous report showed that WT1 was the top ranking from among 75 representative cancer antigens on the basis of nine criteria (4). To date, phase I cancer immunotherapy clinical studies that targeted the WT1 protein have been conducted for AML, MDS, lung, and breast cancer (22,23,31) and phase I/II clinical studies using WT1 peptides have been conducted for patients with various types of cancer (29). It was reported that the increase in the numbers of WT1-specific CTLs in cancer patients after vaccination with WT1 peptides closely correlates with the therapeutic efficacy against cancer (7,16,17,20).…”

Section: Methodsmentioning

confidence: 99%

Establishment of a stable T lymphoma cell line transduced with HLA-A^|^lowast;24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring

et al. 2013

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Wilms' tumor gene 1 (WT1) has been proposed as an attractive target for cancer immunotherapy. A natural 9-mer peptide (CYTWNQMNL), which bound to human leukocyte antigen (HLA)-A*24:02, was identified from among WT1-specific cytotoxic T lymphocyte (CTL) epitopes. This natural WT1 CTL epitope peptide was further modified (CMTWNQMNL) to enhance its binding affinity to HLA-A*24:02. This modified WT1 CTL epitope peptide was superior to the natural peptide for inducing HLA-A*24:02-restricted WT1-specific CTLs. Here we induced several WT1 CTLs that reacted with both modified and natural WT1 tetramers from peripheral blood mononuclear cells. Then, T-cell receptor (TCR) genes were isolated from these WT1 CTLs to determine their Vα and Vβ usage. These TCR genes were transduced into human T lymphoma cells to establish a stable cell line, SK37, which expressed a WT1-specific TCR. We confirmed that SK37 cells reacted with both modified and natural WT1 tetramers, which indicated that SK37 cells could be a useful tool for WT1 tetramer reagent quality assurance. One the basis of these findings, we propose that this WT1 tetramer, which was quality-assured using established SK37 cells, will contribute to reliable immunomonitoring of tumor-specific CTL responses of cancer patients who receive WT1-targeted cancer vaccine therapy or TCR-gene therapy.

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WT1 Peptide‐Based Immunotherapy for Patients with Lung Cancer: Report of Two Cases

Cited by 64 publications

References 31 publications

Immunohistochemical detection of WT1 protein in a variety of cancer cells

Immunohistochemical detection of WT1 protein in a variety of cancer cells

Safety and tolerability evaluation of the use of Montanide ISA™51 as vaccine adjuvant: A systematic review

Establishment of a stable T lymphoma cell line transduced with HLA-A^|^lowast;24:02-restricted WT1-specific TCR genes and its application to antigen-specific immunomonitoring

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