Active immunotherapy for advanced intracranial murine tumors by using dendritic cell-tumor cell fusion vaccines

Kjærgaard, Jørgen; Wang, Li Xin; Kuriyama, Hideyuki; Shu, Suyu; Plautz, Gregory E.

doi:10.3171/jns.2005.103.1.0156

Cited by 57 publications

(33 citation statements)

References 44 publications

(50 reference statements)

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“…Although this vaccine modality is exceptional for its capacity to bypass the constraints of exogenous processing to present endogenous tumor proteins in both MHC Class I-and II-restricted, and highly costimulatory contexts, vaccination has consistently benefited from parenteral codelivery of third signals for maximized therapeutic efficacy. Among tested parenteral third signals, IL-12 and OX40 ligating monoclonal antibody (mAb) have proved particularly effective (10,11). Here, we show that fusion hybrid vaccination plus a single TLR agonist induces no detectable therapeutic antitumor immunity, whereas vaccination plus paired TLR agonists show powerful therapeutic responses against established lung metastases derived from the MCA205 sarcoma.…”

Section: Introductionmentioning

confidence: 92%

Paired Toll-like Receptor Agonists Enhance Vaccine Therapy through Induction of Interleukin-12

et al. 2008

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Minimal requirements for generating effective immunity include the delivery of antigenic (signal 1) and costimulatory (signal 2) signals to T lymphocytes. Recently, a class of third signals, often delivered by antigen-presenting dendritic cells, has been shown to greatly enhance immune responses, especially against tumors. Among signal 3 factors, interleukin (IL)-12 is particularly effective and can be conditionally induced by agonists of Toll-like transmembrane receptors (TLR). In this study, we assessed the therapeutic effect of adjuvant TLR agonist administration upon the capacity of dendritic cell (DC)-tumor electrofusion hybrids to eradicate established MCA205 sarcomas in syngeneic mice. Paired, but not solitary combinations of polyinosine:polycytadilic acid (P[I:C]; TLR3 agonist) and CpG DNA (ODN1826l; TLR9 agonist) stimulated IL-12 secretion from DCs in vitro and synergized with vaccination to achieve potent tumor rejection. Therapeutic effects, however, required coadministration of paired TLR agonists and DC-tumor fusion hybrids. The administration of TLR agonists alone or with fusion vaccine induced transient splenomegaly but without apparent toxicity. The therapeutic effects of this immunization regimen were significantly abrogated through the neutralization of IL12p70, indicating that production of this third signal was essential to the observed tumor regression. These results show the profound functional consequences of TLR cooperativity and further highlight the critical role of IL-12 in antitumor immunity. [Cancer Res 2008;68(11):4045-9]

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Section: Introductionmentioning

confidence: 92%

Paired Toll-like Receptor Agonists Enhance Vaccine Therapy through Induction of Interleukin-12

et al. 2008

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“…Current treatment methods include surgical resection, radio-surgical, external irradiation, chemotherapy (Cheng et al, 2005;Stupp et al, 2006;Wen et al, 2006), and biological therapy (Kjaergaard et al, 2005). Despite recent advances in diagnostics and treatments, prognosis for patients with this disease remains poor (Ng et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Radixin Knockdown by RNA Interference Suppresses Human Glioblastoma Cell Growth in Vitro and in Vivo

Qin¹,

Wang²,

Du³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Radixin, a member of the ERM (ezrin-radixin-moesin) family, plays important roles in cell motility, invasion and tumor progression. It is expressed in a variety of normal and neoplastic cells, including many types of epithelial and lymphoid examples. However, its function in glioblastomas remains elusive. Thus, in this study, radixin gene expression was first examined in the glioblastoma cells, then suppressed with a lentivirus-mediated short-hairpin RNA (shRNA) method.We found that there were high levels of radixin expression in glioblastoma U251cells. Radixin shRNA caused down-regulation of radixin gene expression and when radixin-silenced cells were implanted into nude mice, tumor growth was significantly inhibited as compared to blank control cells or nonsense shRNA cells. In addition, microvessel density in the tumors was significantly reduced. Thrombospondin-1 (TSP-1) and E-cadherin were up-regulated in radixin-suppressed glioblastoma U251 cells. In contrast, MMP9 was down-regulated. Taken together, our findings suggest that radixin is involved in GBM cell migration and invasion, and implicate TSP-1, E-cadherin and MMP9 as metastasis-inducing factors.

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“…36,39,51,52 Others have shown that DC-vaccination combines favorably with radiotherapy by increasing radio-sensitivity of tumor cells and up-regulating the expression of MHC antigens in animal models. 27 In contrast, Chang et al 43 argue that the development of radiotherapy-induced mutant tumor cells, immunologically diverse from the ones obtained during surgery, may render vaccines inactive against residual or relapsed tumors.…”

Section: Timing Of Vaccinationmentioning

confidence: 99%

“…26 Other research has focused on the interaction between other treatment modalities, such as radiotherapy, and DC-vaccinations in murine brain tumor models. 27 It was found that the combination of radiotherapy and DC-vaccinations can enhance the effect of the latter and improve outcomes. This was attributed to irradiation-induced upregulation of MHC molecules in tumor cells, which rendered them better immunological targets.…”

Section: Origin and Research Basis For Efficacy Of The Productmentioning

confidence: 99%

DCVax®-L—Developed by Northwest Biotherapeutics

Polyzoidis

Ashkan

2014

Human Vaccines & Immunotherapeutics

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Active immunotherapy for advanced intracranial murine tumors by using dendritic cell-tumor cell fusion vaccines

Abstract: These data indicate a strategy to achieve an antitumor response against tumors in the central nervous system that is highly focused from both immunological and anatomical perspectives.

Cited by 57 publications

References 44 publications

Paired Toll-like Receptor Agonists Enhance Vaccine Therapy through Induction of Interleukin-12

Paired Toll-like Receptor Agonists Enhance Vaccine Therapy through Induction of Interleukin-12

Radixin Knockdown by RNA Interference Suppresses Human Glioblastoma Cell Growth in Vitro and in Vivo

DCVax®-L—Developed by Northwest Biotherapeutics

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