WT1 vaccine

A patient with bilateral ovarian cancer, peritoneal dissemination, and multiple liver and lung metastases was found with a sudden accumulation of ascites six months after delivery. Chemotherapy was started, but the prognosis was judged to be poor, so immuno-cell therapy was combined with chemotherapy. After multiple cycles of Wilms' tumor antigen 1 (WT1) dendritic cell vaccine therapy and highly activated natural killer (NK) cell therapy, the patient showed a disappearance of ascites and a remarkable reduction of multiple cancers in the whole body...

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) and paediatric high-grade glioma (pHGG) are aggressive glial tumours, for which conventional treatment modalities fall short. Dendritic cell (DC)-based immunotherapy is being investigated as a promising and safe adjuvant therapy. The Wilms' tumour protein (WT1) is a potent target for this type of antigen-specific immunotherapy and is overexpressed in DIPG and pHGG. Based on this, we designed a non-randomised phase I/II trial, assessing the feasibility and safety of WT1 mRNA-loaded DC (WT1/DC) immunotherapy in combination with conventional treatment in pHGG and DIPG...

BACKGROUND AIMS: Acute myeloid leukemia (AML) is classified as a hematologic malignancy characterized by the proliferation of immature blood cells within the bone marrow (BM), resulting in an aberrant and unregulated cellular growth. The primary therapeutic modalities for AML include chemotherapy and hematopoietic stem cell transplantation. However, it is important to note that these treatments are accompanied by important adverse effects and mortality rates. Therefore, the need for more effective treatment options seems necessary, and dendritic cell (DC) vaccine therapy can be one of these options...

INTRODUCTION: The peptide-based cancer vaccine targeting Wilms' tumor 1 (WT1) is a promising immunotherapeutic strategy for hematological malignancies. It remains unclear how long and to what extent the WT1-specific CD8 + cytotoxic T cell (CTL) persist after WT1 peptide vaccination. METHODS: The WT1 peptide vaccine was administered with written consent to a patient with CML in the chronic phase who did not respond well to imatinib, and the patient was followed for 12 years after vaccination...

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...

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...

INTRODUCTION: It is a well-known fact that anti-tumor immunity is a crucial long-term survival factor in cancer. Wilms' tumor 1 (WT1) dendritic cell vaccine therapy (WT1-DC) is an immuno-cell therapy that has been implemented against various cancers as a tumor-specific immunotherapy targeting the common cancer antigen WT1. METHODS: Seven doses of WT1-DC vaccine were administered to six patients, three of whom had stage IV lung cancer with metastases and the other three had stage IV pancreatic cancer with metastases, all of whom were receiving chemotherapy and had similar physical conditions...

In advanced lung adenocarcinoma with metastases, the current standard of care does not in principle include aggressive cancer treatment with surgery and radiotherapy. Therefore, when chemotherapy cannot be continued, the patient is generally switched to palliative care. Our patient with stage IV lung adenocarcinoma in his 60s was receiving chemotherapy, which had to be discontinued due to severe side effects. As standard treatment was no longer indicated, he underwent radioimmunotherapy combined with WT1 dendritic cell vaccine therapy...

WT1-pulsed dendritic cell (WT1-DC) therapy was performed for end-stage squamous cell lung cancer that rapidly worsened soon after completion of carboplatin and paclitaxel. A rapid improvement in immune profile was observed with the initiation of WT1-DC. Docetaxel and ramucirumab were initiated as second-line agents during WT1-DC. The improvement of the immune profile status continued, and at the same time, the cancer showed a predominant shrinkage. Progression-free survival was over 577 days, and the patient was able to lead a normal daily life with a performance status of 1...

The host genetic makeup plays a significant role in causing the within-breed variation among individuals after vaccination. The present study was undertaken to elucidate the genetic basis of differential immune response between high and low responder Landlly (Landrace X Ghurrah) piglets vis-à-vis CSF vaccination. For the purpose, E2 antibody response against CSF vaccination was estimated in sampled animals on the day of vaccination and 21-day post-vaccination as a measure of humoral immune response. Double-digestion restriction associated DNA (ddRAD) sequencing was undertaken on 96 randomly chosen Landlly piglets using Illumina HiSeq platform...

Intensive induction chemotherapy achieves complete remissions (CR) in >60% of patients with acute myeloid leukemia (AML) but overall survival (OS) is poor for relapsing patients not eligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Oral azacytidine may be used as maintenance treatment in AML in first remission, but can be associated with substantial side effects, and less toxic strategies should be explored. Twenty AML patients in first CR (CR1) ineligible for allo-HSCT were treated with FDC101, an autologous RNA-loaded mature dendritic cell (mDC) vaccine expressing two leukemia-associated antigens (LAAs)...

Recently, immune checkpoint inhibitor (ICI) based combination therapies, including anti-PD-1 antibody, nivolumab with anti-CTLA-4 antibody, and ipilimumab have become the primary treatment option for metastatic or unresectable renal cell carcinoma (RCC). However, despite the combination of two ICIs, 60-70% of patients are still resistant to first-line cancer immunotherapy. In the present study, undertook combination immunotherapy for RCC using an oral cancer vaccine (Bifidobacterium longum displaying WT1 tumor associated antigen (B...

We previously conducted a randomized phase II trial of OCV-501, a WT1 peptide presented by helper T cells, in elderly AML (acute myeloid leukemia) patients in first remission, indicating no difference in 2-year disease-free survival (DSF) between the OCV-501 and placebo groups. Here, we analyzed 5-year outcome and biomarkers. Five-year DFS was 36.0% in the OCV-501 group (N = 52) and 33.7% in the placebo group (N = 53), with no significant difference (p = 0.74). The peripheral WT1 mRNA levels were marginally suppressed in the OCV-501 group compared with the placebo group...

(1) Background: EWS fusion genes are associated with Ewing sarcoma and other Ewing family tumors including desmoplastic small round tumor, DSRCT. We utilize a clinical genomics workflow to reveal real-world frequencies of EWS fusion events, cataloging events that are similar, or divergent at the EWS breakpoint. (2) Methods: EWS fusion events from our next-generation sequencing panel (NGS) samples were first sorted by breakpoint or fusion junctions to map out the frequency of breakpoints. Fusion results were illustrated as in-frame fusion peptides involving EWS and a partner gene...

We examined the safety and immunogenicity of sequential administration of a tetravalent, non-HLA (human leukocyte antigen) restricted, heteroclitic Wilms' Tumor 1 (WT1) peptide vaccine (galinpepimut-S) with anti-PD-1 (programmed cell death protein 1) nivolumab. This open-label, non-randomized phase I study enrolled patients with WT1-expressing ovarian cancer in second or third remission from June 2016 to July 2017. Therapy included six (every two weeks) subcutaneous inoculations of galinpepimut-S vaccine adjuvanted with Montanide, low-dose subcutaneous sargramostim at the injection site, with intravenous nivolumab over 12 weeks, and up to six additional doses until disease progression or toxicity...

Traditional vaccinations need to be injected with needles, and since some people have a strong aversion to needles, a needle-free alternative delivery system is important. In this study, we employed ionic liquids (ILs) for transcutaneous delivery of cancer antigen-derived peptides to obtain anticancer therapeutic effects in a needle-free manner. ILs successfully increased the in vitro skin permeability of a peptide from Wilms tumor 1 (WT1), one of the more promising cancer antigens, plus or minus an adjuvant, resiquimod (R848), a toll-like receptor 7 agonist...

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...

Dendritic cells (DC) are powerful cells that play critical roles in anti-tumor immunity, and their use in cancer immunotherapy unlocks hidden capabilities as an effective therapeutic. In order to maximize the full potential of DC, we developed a DC vaccine named CellgramDC-WT1 (CDW). CDW was pulsed with WT1, an antigen commonly expressed in solid tumors, and induced with zoledronate to aid DC maturation. Although our previous study focused on using Rg3 as an inducer of DC maturation, problems with quality control and access led us to choose zoledronate as a better alternative...

No standard treatment has been established for most rare cancers. Here, we report a clinical trial of a biweekly WT1 tri-peptide-based vaccine for recurrent or advanced rare cancers. Due to the insufficient number of patients available for a traditional clinical trial, the trial was designed for rare cancers expressing shared target molecule WT1. The recruitment criteria included WT1-expressing tumors as well as HLA-A*24:02 or 02:01. The primary endpoints were immunoglobulin G (IgG) antibody (Ab) production against the WT1-235 cytotoxic T lymphocyte (CTL) epitope and delayed-type hypersensitivity (DTH) skin reactions to targeted WT1 CTL epitopes...

BACKGROUND/AIM: The prognosis of recurring and metastatic head and neck squamous cell carcinoma (HNSCC) is poor. Although immune checkpoint inhibitors have expanded the treatment options for HNSCC, the response rates are low. Alternatively, cancer vaccines and T-cell therapies are being developed. Identification of useful common cancer antigens and confirmation of human leukocyte antigen (HLA) class I expression are required. MATERIALS AND METHODS: Immunohistochemistry analyses were performed for 10 antigens (FOXM1, TGFBI, SPARC, HSP105α, WT1, AFP, GPC3, PP-RP, KIF20A, KM-HN-1) and HLA class I using specimens of 56 surgical cases...