Identification of mouse helper epitopes for WT1-specific CD4+ T cells

Nakajima, Hiroyuki; Nakata, Jun; Imafuku, Kanako; Hayashibara, Hiromu; Isokawa, Kazuki; Udaka, Keiko; Fujiki, Fumihiro; Morimoto, Soyoko; Hasegawa, Kana; Hosen, Naoki; Hashii, Yoshiko; Nishida, Sumiyuki; Tsuboi, Akihiro; Oka, Y.; Oji, Yusuke; Sogo, Shinji; Sugiyama, Haruo

doi:10.1007/s00262-021-03003-5

Cited by 3 publications

(5 citation statements)

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“…Nakajima et al reported that MHC class II-restricted, WT1 protein-derived helper epitopes—WT1 35 , WT1 86 , and WT1 294 for WT1-speicific CD4 + T cells—play an essential role in WT1-specific tumor immunity in in vivo mouse models [ 15 ]. Among these, we selected WT1 35 as an epitope with the most potent IFN-γ-producing capability of CD4 + T cells that strengthen the CTL-induced WT1-specific lysis of RMAS cells pulsed with WT1 35–52 peptide, suggesting its great potential of inducing CD4 + T cell help that provides critical cellular and molecular mechanisms in CTL responses in cancer immunotherapy [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

“…Previously, an oral vaccine, B. longum 420 was developed, in which the intestinal bacterial strain was used as a vector for WT1 protein [ 14 ]; the vaccine exhibited anticancer activity in mice. However, B. longum 420 had a drawback of not containing a major histocompatibility complex (MHC) class II-restricted epitope important in the induction of WT1-specific Th1 response [ 15 ]. To overcome the drawback, we newly developed B. longum 2656 that contains the CD4 + cell help-inducing, MHC class II-restricted helper epitope (WT1 amino acid sequences 35–52 WAPVLDFAPPGASAYGSL).…”

Section: Introductionmentioning

confidence: 99%

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Enhanced antitumor activity of a novel, oral, helper epitope-containing WT1 protein vaccine in a model of murine leukemia

et al. 2023

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Background A Wilms’ tumor 1 (WT1) oral vaccine, Bifidobacterium longum (B. longum) 420, in which the bacterium is used as a vector for WT1 protein, triggers immune responses through cellular immunity consisting of cytotoxic T lymphocytes (CTLs) and other immunocompetent cells (e.g., helper T cells). We developed a novel, oral, helper epitope-containing WT1 protein vaccine (B. longum 2656) to examine whether or not B. longum 420/2656 combination further accelerates the CD4+ T cell help-enhanced antitumor activity in a model of murine leukemia. Methods C1498-murine WT1—a genetically-engineered, murine leukemia cell line to express murine WT1—was used as tumor cell. Female C57BL/6 J mice were allocated to the B. longum 420, 2656, and 420/2656 combination groups. The day of subcutaneous inoculation of tumor cells was considered as day 0, and successful engraftment was verified on day 7. The oral administration of the vaccine by gavage was initiated on day 8. Tumor volume, the frequency and phenotypes of WT1-specific CTLs in CD8+ T cells in peripheral blood (PB) and tumor-infiltrating lymphocytes (TILs), as well as the proportion of interferon-gamma (INF-γ)-producing CD3+CD4+ T cells pulsed with WT135–52 peptide in splenocytes and TILs were determined. Results Tumor volume was significantly smaller (p < 0.01) in the B. longum 420/2656 combination group than in the B. longum 420 group on day 24. WT1-specific CTL frequency in CD8+ T cells in PB was significantly greater in the B. longum 420/2656 combination group than in the B. longum 420 group at weeks 4 (p < 0.05) and 6 (p < 0.01). The proportion of WT1-specific, effector memory CTLs in PB increased significantly in the B. longum 420/2656 combination group than in the B. longum 420 group at weeks 4 and 6 (p < 0.05 each). WT1-specific CTL frequency in intratumoral CD8+ T cells and the proportion of IFN-γ-producing CD3+CD4+ T cells in intratumoral CD4+ T cells increased significantly (p < 0.05 each) in the B. longum 420/2656 combination group than in the 420 group. Conclusions B. longum 420/2656 combination further accelerated antitumor activity that relies on WT1-specific CTLs in the tumor compared with B. longum 420.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Enhanced antitumor activity of a novel, oral, helper epitope-containing WT1 protein vaccine in a model of murine leukemia

et al. 2023

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“…However, subsequent mouse experiments indicated the potential usefulness of major histocompatibility complex (MHC) class II antigen-restricted peptides (helper peptides). 4 , 13 , 14 Recently, trials using both CTL and helper peptides have been conducted, and improvements in clinical outcomes have been reported 15–17 ( Table 1 ).…”

Section: Utilization Of Vaccines With Helper Peptidesmentioning

confidence: 99%

“…Several preclinical studies have focused on enhancing the effectiveness of the WT1 peptide or DC vaccines, highlighting advancements in areas such as the identification of mouse helper peptide, 13 , 14 cord blood-derived DC vaccine, 51 oral vaccines facilitated by intestinal immunity, 52 innovative adjuvants, 53 improvements in peptide transport, 54 and enhancement of antigen uptake and presentation by DCs 55 , 56 ( Table 4 ).…”

Section: Recent Preclinical Developmentsmentioning

confidence: 99%

“…Nakajima et al identified mouse helper peptides (WT1 35-52, WT1 86-102, WT1 294-312) and examined their efficacy in a vaccine incorporating them. 13 Compared with vaccines with CTL epitopes alone, vaccines containing both CTL and helper peptides induced and maintained more potent WT1-specific CTLs and facilitated the rejection of WT1-expressing tumors. Importantly, the WT1-specific CD4 + T cells induced by this combined vaccine not only activated WT1-specific CD8 + T cells but also played a vital role in the migration and infiltration of CD8 + T cells into the tumor.…”

Section: Identification Of Mouse Helper Peptidementioning

confidence: 99%

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Wilms’ tumor 1 -targeting cancer vaccine: Recent advancements and future perspectives

Ogasawara

2023

Human Vaccines & Immunotherapeutics

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This mini-review explores recent advancements in cancer vaccines that target Wilms’ tumor (WT1). Phase I/II trials of WT1 peptide vaccines have demonstrated their safety and efficacy against various cancers. Early trials employing HLA class I peptides evolved through their combination with HLA class II peptides, resulting in improved clinical outcomes. Additionally, WT1-targeted dendritic cell vaccines have exhibited favorable results. Studies focusing on hematological malignancies have revealed promising outcomes, including long-term remission and extended survival times. The combination of vaccines with immune checkpoint inhibitors has shown synergistic effects. Current preclinical developments are focused on enhancing the effectiveness of WT1 vaccines, underscoring the necessity for future large-scale Phase III trials to further elucidate their efficacy.

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Dendritic cell vaccination in combination with erlotinib in a patient with inoperable lung adenocarcinoma: a case report

Kosumi,

Kobayashi,

Shimodaira

et al. 2024

J Med Case Reports

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Background Satisfactory treatment for patients with unresectable advanced lung cancer has not yet been established. We report a case of unresectable advanced lung cancer (stage IIIb: T2aN3M0) treated with a total of 15 doses of dendritic cells pulsed with a Wilms’ tumor 1 and mucin 1 vaccine in combination with erlotinib, a small molecule epidermal growth factor receptor tyrosine kinase inhibitor, for more than 699 days without recurrence or metastasis. Case presentation A 63-year-old Korean woman was diagnosed with lung adenocarcinoma by pathology and computed tomography. The adenocarcinoma showed an epidermal growth factor receptor (EGFR) mutation, no anaplastic lymphoma kinase expression, and less than 1% expression of programmed death ligand 1. She received erlotinib alone for approximately 1 month. She then received erlotinib and the dendritic cells pulsed with Wilms’ tumor 1 and mucin 1 vaccine. The diameter of the erythema at the vaccinated sites was 30 mm at 48 hours after the first vaccination. Moreover, it was maintained at more than 20 mm during the periods of vaccination. These results suggested the induction of antitumor immunity by the vaccine. Remarkably, the tumor size decreased significantly to 12 mm, a 65.7% reduction, after combined therapy with eight doses of the dendritic cells pulsed with Wilms’ tumor 1 and mucin 1 vaccine and erlotinib for 237 days based on fluorodeoxyglucose uptake by positron emission tomography/computed tomography and computed tomography. Interestingly, after 321 days of combination therapy, the clinical findings improved, and no tumor was detected based on computed tomography. Validation of the tumor’s disappearance persisted for at least 587 days after treatment initiation, without any indication of recurrence or metastasis. Conclusion Standard anticancer therapy combined with the dendritic cells pulsed with Wilms’ tumor 1 and mucin 1 vaccine may have therapeutic effects for such patients with unresectable lung adenocarcinoma.

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Identification of mouse helper epitopes for WT1-specific CD4+ T cells

Cited by 3 publications

References 43 publications

Enhanced antitumor activity of a novel, oral, helper epitope-containing WT1 protein vaccine in a model of murine leukemia

Enhanced antitumor activity of a novel, oral, helper epitope-containing WT1 protein vaccine in a model of murine leukemia

Wilms’ tumor 1 -targeting cancer vaccine: Recent advancements and future perspectives

Dendritic cell vaccination in combination with erlotinib in a patient with inoperable lung adenocarcinoma: a case report

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