Adjuvant Immunotherapy with Whole-Cell Lysate Dendritic Cells Vaccine for Glioblastoma Multiforme: A Phase II Clinical Trial

Cho, Der Yang; Yang, Wen; Lee, Han Chung; Hsu, Den Mei; Lin, Hung Lin; Lin, Shinn Zong; Chen, Chun-Chung; Harn, Horng Jyh; Liu, Chun Lin; Lee, Wen Yuan; Ho, Li Hui

doi:10.1016/j.wneu.2011.08.020

Cited by 127 publications

(121 citation statements)

References 28 publications

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“…Maximal increase, 143.6 weeks, was achieved by Prins et al [70]. Similar values were obtained by Cho et al [71] and Fadul et al [72]: 127.6 and 112 weeks, respectively.…”

Section: Based Vaccinessupporting

confidence: 83%

Recent news in the glioblastoma research

Rybalkina¹,

Pavlova

Stavrovskaya³

2015

Biochem. Moscow Suppl. Ser. A

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Glioblastoma multiforme (GBL) is the most frequent and aggressive tumor of the brain. Mean sur vival time of GBL patients is only 12-15 months, despite most intensive treatments. To fight this severe, still almost incurable disease, a great number of researches are recruited. Here we review the results of the GBL investigations published recently (from the end of 2013 to the first half of 2014) that ensured a considerable progress in this field of oncology. Combination of DNA and RNA sequencing and functional validation made it possible to define a somatic genomic landscape of GBL, to uncover new genetic driver alterations in GBL, and to suggest new approaches for the treatment of GBL. The results of the GBL immunotherapy are discussed.

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“…Maximal increase, 143.6 weeks, was achieved by Prins et al [70]. Similar values were obtained by Cho et al [71] and Fadul et al [72]: 127.6 and 112 weeks, respectively.…”

Section: Based Vaccinessupporting

confidence: 83%

Recent news in the glioblastoma research

Rybalkina¹,

Pavlova

Stavrovskaya³

2015

Biochem. Moscow Suppl. Ser. A

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“…The use of autologous ex vivo pulsed DCs in patients diagnosed with GBM has also been deemed feasible and well tolerated with encouraging clinical responses [17], [18]. Administration of primed DCs to GBM patients was associated with the induction of measurable systemic CTL responses and modest increases in survival.…”

Section: Introductionmentioning

confidence: 99%

Assessing the Role of STAT3 in DC Differentiation and Autologous DC Immunotherapy in Mouse Models of GBM

et al. 2014

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Cellular microenvironments, particularly those found in tumors, elicit a tolerogenic DC phenotype which can attenuate immune responses. Central to this process is the STAT3-mediated signaling cascade. As a transcription factor and oncogene, STAT3 promotes the expression of genes which allow tumor cells to proliferate, migrate and evade apoptosis. More importantly, activation of STAT3 in tumor infiltrating immune cells has been shown to be responsible, in part, for their immune-suppressed phenotype. The ability of STAT3 to orchestrate a diverse set of immunosuppressive instructions has made it an attractive target for cancer vaccines. Using a conditional hematopoietic knockout mouse model of STAT3, we evaluated the impact of STAT3 gene ablation on the differentiation of dendritic cells from bone marrow precursors. We also assessed the impact of STAT3 deletion on phagocytosis, maturation, cytokine secretion and antigen presentation by GM-CSF derived DCs in vitro. In addition to in vitro studies, we compared the therapeutic efficacy of DC vaccination using STAT3 deficient DCs to wild type counterparts in an intracranial mouse model of GBM. Our results indicated the following pleiotropic functions of STAT3: hematopoietic cells which lacked STAT3 were unresponsive to Flt3L and failed to differentiate as DCs. In contrast, STAT3 was not required for GM-CSF induced DC differentiation as both wild type and STAT3 null bone marrow cells gave rise to similar number of DCs. STAT3 also appeared to regulate the response of GM-CSF derived DCs to CpG. STAT3 null DCs expressed high levels of MHC-II, secreted more IL-12p70, IL-10, and TNFα were better antigen presenters in vitro. Although STAT3 deficient DCs displayed an enhanced activated phenotype in culture, they elicited comparable therapeutic efficacy in vivo compared to their wild type counterparts when utilized in vaccination paradigms in mice bearing intracranial glioma tumors.

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“…Mature DCs can be used as vaccines after in vitro tumor peptide loading or after their immature DC precursors were initially loaded with tumor protein or lysate and matured thereafter. [64][65][66][67][68] To resolve this problem, immunomodulatory combined action of MENK and PTD on DCs was detected in this study. The results indicated that the combination of MENK with PTD induced morphological, phenotypic and functional maturation of DCs derived from mouse bone marrow cells.…”

Section: Discussionmentioning

confidence: 99%