Clinical Application of a Dendritic Cell Vaccine Raised Against Heat-Shocked Glioblastoma

Jie, Xiaohua; Hua, Limei; Jiang, Weihao; Fěng, Fang; Feng, Ge; Hua, Z.

doi:10.1007/s12013-011-9265-6

Cited by 74 publications

(65 citation statements)

References 23 publications

(26 reference statements)

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“…The majority of vaccinations were started within 1 week to 3 months after resection. 3,4,16,32 However, previous reports did not describe the time of initiation of vaccination in detail. 4 In our study, 5 of 6 patients with glioblastoma had PD at the end of the first session of vaccination.…”

Section: Discussionmentioning

confidence: 99%

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Dendritic cell–based immunotherapy targeting Wilms’ tumor 1 in patients with recurrent malignant glioma

Sakai

Shimodaira

Maejima³

et al. 2015

JNS

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abbreviatioNs CTL = cytotoxic T lymphocyte; DC = dendritic cell; HLA = human leukocyte antigen; IL = interleukin; Ke = kiloequivalent; KPS = Karnofsky Performance Scale; MST = median overall survival time; PD = progressive disease; PR = partial response; RECIST = Response Evaluation Criteria in Solid Tumors; SD = stable disease; TAA = tumor-associated antigen; WT1 = Wilms' tumor 1. Department of Neurosurgery, National Hospital Organization, Shinshu Ueda Medical Center, Ueda, Nagano, Japan obJect Dendritic cell (DC)-based vaccination is considered a potentially effective therapy against advanced cancer. The authors conducted a Phase I study to investigate the safety and immunomonitoring of Wilms' tumor 1 (WT1)-pulsed DC vaccination therapy for patients with relapsed malignant glioma. methods WT1-pulsed and/or autologous tumor lysate-pulsed DC vaccination therapy was performed in patients with relapsed malignant gliomas. Approximately 1 × 10 7 to 2 × 10 7 pulsed DCs loaded with WT1 peptide antigen and/or tumor lysate were intradermally injected into the axillary areas with OK-432, a streptococcal preparation, at 2-week intervals for at least 5-7 sessions (1 course) during an individual chemotherapy regimen. results Ten patients (3 men, 7 women; age range 24-64 years [median 39 years]) with the following tumors were enrolled: glioblastoma (6), anaplastic astrocytoma (2), anaplastic oligoastrocytoma (1), and anaplastic oligodendroglioma (1). Modified WT1 peptide-pulsed DC vaccine was administered to 7 patients, tumor lysate-pulsed DC vaccine to 2 patients, and both tumor lysate-pulsed and WT1-pulsed DC vaccine to 1 patient. The clinical response was stable disease in 5 patients with WT1-pulsed DC vaccination. In 2 of 5 patients with stable disease, neurological findings improved, and MR images showed tumor shrinkage. No serious adverse events occurred except Grade 1-2 erythema at the injection sites. WT1 tetramer analysis detected WT1-reactive cytotoxic T cells after vaccination in patients treated with WT1-pulsed therapy. Positivity for skin reaction at the injection sites was 80% (8 of 10 patients) after the first session, and positivity remained for these 8 patients after the final session. coNclusioNs This study of WT1-pulsed DC vaccination therapy demonstrated safety, immunogenicity, and feasibility in the management of relapsed malignant gliomas.

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Section: Discussionmentioning

confidence: 99%

“…Recent Phase I and II studies demonstrated the safety and efficacy of DC vaccination against malignant gliomas. 5,16,36 Vaccination with DCs was also studied in 313 patients with high-grade gliomas. 44 The antigen sources were tumor lysate, peptides eluted from autologous tumor cells, defined peptides, and autologous tumor cells.…”

mentioning

confidence: 99%

Dendritic cell–based immunotherapy targeting Wilms’ tumor 1 in patients with recurrent malignant glioma

Sakai

Shimodaira

Maejima³

et al. 2015

JNS

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“…Significantly, adverse events were limited to transient elevations in liver transaminases with no secondary autoimmune disease [39–43]. In a similar trial with 25 randomized patients, DC vaccination with heat shocked autologous tumor lysate delayed tumor recurrence compared to a control cohort, increased levels of peripheral T cells (CD3 + , CD4 + , CD8 + ), and NK cells, and restored CD4:CD8 ratios [44]. Response of peripheral lymphocytes to cytokine stimulation via pSTAT signaling was later identified as a potential predictor of two-year survival and therapeutic efficacy [45].…”

Section: Targeting Immunosuppression In Gbmmentioning

confidence: 99%

Biomarkers for glioma immunotherapy: the next generation

et al. 2015

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The term “biomarker” historically refers to a single parameter, such as the expression level of a gene or a radiographic pattern, used to indicate a broader biological state. Molecular indicators have been applied to several aspects of cancer therapy: to describe the genotypic and phenotypic state of neoplastic tissue for prognosis, to predict susceptibility to anti-proliferative agents, to validate the presence of specific drug targets, and to evaluate responsiveness to therapy. For glioblastoma (GBM), immunohistochemical and radiographic biomarkers accessible to the clinical lab have informed traditional regimens, but while immunotherapies have emerged as potentially disruptive weapons against this diffusely infiltrating, heterogeneous tumor, biomarkers with strong predictive power have not been fully established. The cancer immunotherapy field, through the recently accelerated expansion of trials, is currently leveraging this wealth of clinical and biological data to define and revise the use of biomarkers for improving prognostic accuracy, personalization of therapy, and evaluation of responses across the wide variety of tumors. Technological advancements in DNA sequencing, cytometry, and microscopy have facilitated the exploration of more integrated, high-dimensional profiling of the disease system—incorporating both immune and tumor parameters—rather than single metrics, as biomarkers for therapeutic sensitivity. Here we discuss the utility of traditional GBM biomarkers in immunotherapy and how the impending transformation of the biomarker paradigm—from single markers to integrated profiles—may offer the key to bringing predictive, personalized immunotherapy to GBM patients.

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“…Jie and colleagues recently published data from a clinical trial demonstrating that treatment with autologous DC vaccine increases the circulating pool of T lymphocytes and the release of cytokines (IL-2, IL-12 and IFN-γ), thus suggesting that vaccines can cultivate an immune profile favorable to combating tumor growth [39]. Notably, patients receiving vaccine also had improved tumor control rates, higher quality of life and prolonged survival [39]. More direct efforts to treat with IL-2 supplementation have further highlighted the importance of IL-2 in mounting an immune response against glioma [40].…”

Section: Pi3k Pathway Inhibitors and Interleukinsmentioning

confidence: 99%

PI3K Pathway Inhibitors: Potential Prospects as Adjuncts to Vaccine Immunotherapy for Glioblastoma

Ivan

Sun

et al. 2014

Immunotherapy

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Constitutive activation of the PI3K pathway has been implicated in glioblastoma (GBM) pathogenesis. Pharmacologic inhibition can both inhibit tumor survival and downregulate expression of programmed death ligand-1, a protein highly expressed on glioma cells that strongly contributes to cancer immunosuppression. In that manner, PI3K pathway inhibitors can help optimize GBM vaccine immunotherapy. In this review, we describe and assess the potential integration of various classes of PI3K pathway inhibitors into GBM immunotherapy. While early-generation inhibitors have a wide range of immunosuppressive effects that could negate their antitumor potency, further work should better characterize how contemporary inhibitors affect the immune response. This will help determine if these inhibitors are truly a therapeutic avenue with a strong future in GBM immunotherapy.

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Clinical Application of a Dendritic Cell Vaccine Raised Against Heat-Shocked Glioblastoma

Cited by 74 publications

References 23 publications

Dendritic cell–based immunotherapy targeting Wilms’ tumor 1 in patients with recurrent malignant glioma

Dendritic cell–based immunotherapy targeting Wilms’ tumor 1 in patients with recurrent malignant glioma

Biomarkers for glioma immunotherapy: the next generation

PI3K Pathway Inhibitors: Potential Prospects as Adjuncts to Vaccine Immunotherapy for Glioblastoma

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