Integration of autologous dendritic cell-based immunotherapy in the standard of care treatment for patients with newly diagnosed glioblastoma: results of the HGG-2006 phase I/II trial

Ardon, Hilko; Gool, Stefaan W. Van; Verschuere, Tina; Maes, Wim; Fieuws, Steffen; Sciot, Raf; Wilms, Guido; Demaerel, Philippe; Goffin, Jan; Calenbergh, Frank Van; Menten, Johan; Clément, Paul M.; Dębiec‐Rychter, Maria; Vleeschouwer, Steven De

doi:10.1007/s00262-012-1261-1

Cited by 141 publications

(116 citation statements)

References 38 publications

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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: 91%

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: 91%

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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“…In the past trials, increased peripheral immune markers, such as cytotoxic T-lymphocyte (CTL) activity and positive delayed tissue hypersensitivity (DTH) tests, have been reported, but their correlation with clinical outcomes was weak and therefore they lacked prognostic value. 28,36,38,44,47 Nevertheless Yamanaka et al 37 and Wheeler et al 39 reported some value in measuring such markers, while Fadul et al 44 found that 50% of patients developed a measurable immune response which was associated with improved OS. Currently the most valid indicator of vaccination-induced immune responses to GBM is considered to be tumor infiltration by activated T-cells.…”

Section: Immune Monitoring Of the Productmentioning

confidence: 99%

“…Mean overall survival (OS) ranged between 16.0 and 38.4 months for ND-GBM and between 9.6 and 35.9 months for recurrent GBM. 28, Of interest, Ardon et al 47 analyzed their results based on RPA classification and reported a mean OS of 39.7 months on patients with ND-GBM for RPA class III. Thus, it seems that specific subgroups of GBM patients may benefit from DC-vaccinations greater than others.…”

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confidence: 99%

DCVax®-L—Developed by Northwest Biotherapeutics

Polyzoidis

Ashkan

2014

Human Vaccines & Immunotherapeutics

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“…Dendritic cell based therapeutic approach has now been applied as an adjuvant for the treatment of several types of cancers such as lymphomas (Hsu et al 1996), myelomas (Curti et al, 2007), brain cancers (Ardon et al, 2012) and pediatric malignancies (Dohnal et al, 2007) with some degree of success. Since no uniform standardised protocol has emerged, we developed a protocol and initiated a phase I trial.…”

Section: Discussionmentioning

confidence: 99%

“…A study using DCs against glioma had shown that cytotoxic T cell activity may develop even twelve weeks (Yu et al, 2001) after vaccination while recently another reported CD8+T cell and IFN-γ responses in melanoma patients after they were given multiple DC vaccines loaded with a cocktail of synthetic peptides including MART-1 (Melanoma antigen recognized by autologous T cells-1) (Okoshita et al, 2012). Ardon et al (2012) also noted that DC-based tumor vaccines in booster doses improved the six month progression free and median overall survival of newly diagnosed glioma patients who underwent surgery and concomitant chemoradiotherapy. For sustained stimulation of the immune system through multiple vaccinations, leukapheresis may be the best strategy.…”

Section: Discussionmentioning

confidence: 99%

Development and Clinical Evaluation of Dendritic Cell Vaccines for HPV Related Cervical Cancer - a Feasibility Study

Ramanathan¹,

Ganesarajah²,

Raghanvan³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Human papillomavirus infection (HPV) and HPV related immune perturbation play important roles in the development of cervical cancer. Since mature dendritic cells (DCs) are potent antigen-presenting cells (APC), they could be primed by HPV antigens against cervical cancers. In this study we were able to generate, maintain and characterize, both phenotypically and functionally, patient specific dendritic cells in vitro. A randomized Phase I trial with three arms -saline control (arm I), unprimed mature DC (arm II) and autologous tumor lysate primed mature DC (arm III) and fourteen patients was conducted. According to WHO criteria, grade 0 or grade one toxicity was observed in three patients. One patient who received tumor lysate primed dendritic cells and later cis-platin chemotherapy showed a complete clinical response of her large metastatic disease and remained disease free for more than 72 months. Our findings indicate that DC vaccines hold promise as adjuvant sfor cervical cancer treatment and further studies to improve their efficacy need to be conducted.

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Integration of autologous dendritic cell-based immunotherapy in the standard of care treatment for patients with newly diagnosed glioblastoma: results of the HGG-2006 phase I/II trial

Abstract: Full integration of autologous DC-based tumor vaccination into standard postoperative radiochemotherapy for newly diagnosed glioblastoma seems safe and possibly beneficial. These results were used to power the currently running phase IIb randomized clinical trial.

Cited by 141 publications

References 38 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

DCVax®-L—Developed by Northwest Biotherapeutics

Development and Clinical Evaluation of Dendritic Cell Vaccines for HPV Related Cervical Cancer - a Feasibility Study

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