Induction of Antigen-Specific Cytotoxic T Lymphocytes by Chemoradiotherapy in Patients Receiving Wilms? Tumor 1-Targetted Dendritic Cell Vaccinations for Pancreatic Cancer

Shimodaira, Shigetaka

doi:10.4172/2167-7964.1000196

Cited by 9 publications

(11 citation statements)

References 22 publications

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“…It has also been reported that WT1 antigen expression in pancreatic cancer cell lines is increased by GEM treatment (65). Initial radiotherapy with additional chemotherapeutic drugs acting through their off-target effects may have accelerated the development of acquired cancer immunity and induced antigen-specific CTLs in patients receiving WT1-targeted DC vaccinations (47). Therefore, DC vaccines in combination with chemotherapy and radiotherapy should promote treatment efficacy against advanced disease.…”

Section: Vaccination Technology For Pediatric Patientsmentioning

confidence: 99%

“…Sipuleucel-T (Provenge ® ) is a US Food and Drug Administration-approved autologous DC-based immunotherapy for men with metastatic hormonerefractory prostate cancer, which provides a new treatment option for patients with this type (36)(37)(38). DC vaccines primed with HLA class I-/II-restricted WT1 peptides (WT1-DC) have been determined to be safe and feasible, with few adverse reactions reported by patients with advanced cancers, including lung, breast, stomach, biliary tract, pancreas, ovary, and even high-grade glioma (39)(40)(41)(42)(43)(44)(45)(46)(47). Clinical studies have indicated that the efficacy of DC vaccination may be enhanced by the off-target effects of chemotherapeutic drugs (39)(40)(41)(42)(43)(44)48) and chemoradiotherapy (47,49,50), suggesting a survival benefit in some patients.…”

Section: Introductionmentioning

confidence: 99%

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Dendritic Cell-Based Cancer Immunotherapy Targeting Wilms’ Tumor 1 for Pediatric Cancer

et al. 2016

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The treatment of advanced pediatric cancers that have metastasized to distant organs remains difficult. Investigations evaluating the potential treatment of these cancers using therapeutic vaccination with an active dendritic cell (DC)-based immunotherapy are also being conducted. This method induces an efficient immune response by the acquired immune system against tumor-associated antigens. Cancer vaccination therapies have been prepared using autologous monocyte-derived mature DCs exposed to granulocyte-macrophage colony-stimulating factor Shimodaira et al. 114 and interleukin-4, which are the molecules principally attributed to the presence of tumorassociated antigens. Wilms' tumor 1 (WT1), an attractive target antigen that has been widely detected in cancers including sarcoma and leukemia, has been shown to be the most potent tumor-associated antigen. DC-based immunotherapy targeting WT1 may have a potentially strong therapeutic activity against cancers. DC vaccines primed with human leukocyte antigen (HLA) class I-/II-restricted WT1 peptides (WT1-DC) are a feasible option. A 6-year-old girl with neuroblastoma and a 14-year-old girl with WT received autologous DC vaccination pulsed with a modified WT1 peptide compatible with HLA-A*24:02. The patients received 20 and 25 vaccines, respectively, and experienced no adverse effects aside from a grade 2 skin reaction at the injection site and a fever with tolerable elevation. WT1tetramer analysis after vaccination detected WT1-specific immune responses. This treatment strategy may be safe, tolerable, and even feasible for all patients who are refractory to treatment and for pediatric patients who have relapsed with neoplasms.

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Section: Vaccination Technology For Pediatric Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dendritic Cell-Based Cancer Immunotherapy Targeting Wilms’ Tumor 1 for Pediatric Cancer

et al. 2016

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“…Radiation therapy can also enhance the expression of HLA class I on the surface of cancer cells, boosting the recognition and killing of irradiated cancer cells through T cells and NK cells [24]. DCs in combination with chemoradiotherapy may accelerate the development of acquired cancer immunity to induce antigen-specific cytotoxic T lymphocytes (CTLs) [25,26]. Chemoradiotherapy induce immunogenic cell death, which could trigger T-cell immunity mediated by high-mobility group box 1 protein in patients with oesophageal squamous cell cancer [27].…”

Section: Introductionmentioning

confidence: 99%

An update on Dendritic Cell-Based Cancer Immunotherapy

Shimodaira¹,

Hirabayashi²

2016

Immunome Res

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Although treating advanced cancers that affect organs with distant metastasis remains challenging, the pace of recent advances has accelerated; these advances have particularly focused on the inhibitors of key immune potentiates. Research on therapeutic vaccination involving active dendritic cell (DC)-based immunotherapy is also being performed for the induction of an efficient immune response against cancer-associated antigens by the acquired immune system. Cancer vaccines prepared with autologous monocyte-derived mature DCs have been generated using granulocyte-macrophage colony-stimulating factor and interleukin-4, which are principally attributed to the presence of tumor-associated antigens. Wilms' tumor 1 (WT1) is an attractive target antigen that is widely detected in many cancers. DC-based immunotherapy targeting WT1 may elicit a strong therapeutic response to cancers. DC vaccines primed with HLA class I/II-restricted WT1 peptides (WT1-DC) are a feasible option for patients with advanced cancers. Immune response monitoring using tetramer analysis and/or enzyme-linked immunosorbent spot assay has been applied to determine the efficacy of WT1-DC. The inhibition of immune suppressors and acceleration of anti-cancer immunity with WT1-DC may comprise a promising future therapeutic strategy for treating advanced cancers.

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“…Rather, the clinical efficacy is more evidently demonstrated by the delayed separation of the survival curve with a benefit in terms of prolonged overall survival (OS) [ 31 , 32 ]. The efficacy of DC vaccination may be enhanced by off-target effects of chemotherapeutic drugs, radiotherapy, and chemoradiotherapy [ 33 , 34 , 35 ]. The combination of chemotherapy and/or radiotherapy has been investigated in addition to the period required for adaptation.…”

Section: Introductionmentioning

confidence: 99%

Dendritic Cell-Based Adjuvant Vaccination Targeting Wilms’ Tumor 1 in Patients with Advanced Colorectal Cancer

et al. 2015

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Despite significant recent advances in the development of immune checkpoint inhibitors, the treatment of advanced colorectal cancer involving metastasis to distant organs remains challenging. We conducted a phase I study to investigate the safety and immunogenicity of Wilms’ tumor (WT1) class I/II peptides-pulsed dendritic cell DC vaccination for patients with advanced colorectal cancer. Standard treatment comprising surgical resection and chemotherapy was followed by one course of seven biweekly administrations of 1–2 × 107 DCs with 1–2 KE of OK-432 (streptococcal preparation) in three patients. Clinical efficacy was confirmed based on WT1 expression using immunohistochemistry on paraffin-embedded tissues and immune monitoring using tetramer analysis and enzyme-linked immunosorbent spot (ELISPOT) assays. WT1 expression with human leukocyte antigen (HLA)-class I molecules was detected in surgical resected tissues. Adverse reactions to DC vaccinations were tolerable under an adjuvant setting. WT1-specific cytotoxic T cells were detected by both modified WT1-peptide/HLA-A*24:02 tetramer analysis and/or interferon-γ-producing cells through the use of ELISPOT assays after the first DC vaccination. Immunity acquired from DC vaccination persisted for two years with prolonged disease-free and overall survival. The present study indicated that DC vaccination targeting WT1 demonstrated the safety and immunogenicity as an adjuvant therapy in patients with resectable advanced colorectal cancer.

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Induction of Antigen-Specific Cytotoxic T Lymphocytes by Chemoradiotherapy in Patients Receiving Wilms? Tumor 1-Targetted Dendritic Cell Vaccinations for Pancreatic Cancer

Cited by 9 publications

References 22 publications

Dendritic Cell-Based Cancer Immunotherapy Targeting Wilms’ Tumor 1 for Pediatric Cancer

Dendritic Cell-Based Cancer Immunotherapy Targeting Wilms’ Tumor 1 for Pediatric Cancer

An update on Dendritic Cell-Based Cancer Immunotherapy

Dendritic Cell-Based Adjuvant Vaccination Targeting Wilms’ Tumor 1 in Patients with Advanced Colorectal Cancer

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