preparation-tumor-antigen-loaded-mature-dendritic-cells-for

Preparation of Tumor Antigen-loaded Mature Dendritic Cells for Immunotherapy

While clinical studies have established that antigen-loaded DC vaccines are safe and promising therapy for tumors 1, their clinical efficacy remains to be ...

NYU Langone Medical Center

Glioblastoma is a fatal brain tumor that becomes highly vascularized by secreting proangiogenic factors and depends on continued angiogenesis to increase in size. Consequently, a successful antiangiogenic therapy should provide long-term inhibition of tumor-induced angiogenesis, suggesting long-term gene transfer as a therapeutic strategy. In this study a soluble vascular endothelial growth factor receptor (sFlt-1) and an angiostatin-endostatin fusion gene (statin-AE) were codelivered to human glioblastoma xenografts by nonviral gene transfer using the Sleeping Beauty (SB) transposon. In subcutaneously implanted xenografts, co-injection of both transgenes showed marked anti-tumor activity as demonstrated by reduction of tumor vessel density, inhibition or abolition of glioma growth, and increase in animal survival (P = 0.003). Using luciferase-stable engrafted intracranial gliomas, the anti-tumor effect of convection-enhanced delivery of plasmid DNA into the tumor was assessed by luciferase in vivo imaging. Sustained tumor regression of intracranial gliomas was achieved only when statin-AE and sFlt-1 transposons were coadministered with SB-transposase-encoding DNA to facilitate long-term expression. We show that SB can be used to increase animal survival significantly (P = 0.008) by combinatorial antiangiogenic gene transfer in an intracranial glioma model.

Combinatorial antiangiogenic gene therapy by nonviral gene transfer using the sleeping beauty transposon causes tumor regression and improves survival in mice bearing intracranial human glioblastoma.

Glioblastome est une tumeur de cerveau fatale qui devient fortement vascularis&eacute;e en s&eacute;cr&eacute;tant des facteurs on et d&eacute;pend d&#39;une angiogen&egrave;se continue d&#39;augmenter en taille. Par cons&eacute;quent, un traitement anti-angiog&eacute;nique r&eacute;ussie devrait fournir &agrave; long terme inhibition de l&#39;angiogen&egrave;se induite par la tumeur, ce qui sugg&egrave;re de transfert de g&egrave;nes &agrave; long terme comme une strat&eacute;gie th&eacute;rapeutique. Dans cette &eacute;tude, un r&eacute;cepteur de facteur de croissance endoth&eacute;lial vasculaire soluble (sFlt-1) et un g&egrave;ne de fusion de l&#39;angiostatine-endostatine (statine-AE) ont &eacute;t&eacute; codelivered aux x&eacute;nogreffes de glioblastome humain par transfert de g&egrave;ne de nonviral &agrave; l&#39;aide du transposon Sleeping Beauty (SB). Dans les x&eacute;nogreffes implant&eacute;s par voie sous-cutan&eacute;e, coinjection de deux transg&egrave;nes a montr&eacute; marqu&eacute; une activit&eacute; antitumorale comme en t&eacute;moigne la r&eacute;duction de la densit&eacute; de navire de tumeur, inhibition ou suppression des gliomes croissance et augmentation de la survie animale (P = 0,003). L&#39;effet antitumoral de convection-enhanced delivery de plasmides de QU&#39;ADN dans la tumeur a &eacute;t&eacute; &eacute;valu&eacute; par la lucif&eacute;rase in vivo &agrave; l&#39;aide de gliomes intracr&acirc;niens implant&eacute;es de lucif&eacute;rase-stable, imagerie. Une r&eacute;gression tumorale soutenue des gliomes intracr&acirc;niens a &eacute;t&eacute; atteint que lorsque les transposons statine-AE et sFlt-1 ont &eacute;t&eacute; administr&eacute;s avec SB-transposase-codage ADN afin de faciliter l&#39;expression &agrave; long terme. Nous montrons que SB peut &ecirc;tre utilis&eacute; pour augmenter la survie animale significativement (P = 0,008) par transfert de g&egrave;nes anti-angiog&eacute;niques combinatoire dans un mod&egrave;le de gliomes intracr&acirc;niens.

Th&eacute;rapie g&eacute;nique antiangiog&eacute;nique combinatoire par transfert de g&egrave;ne nonviral &agrave; l&#39;aide du transposon de beaut&eacute; endormie provoque une r&eacute;gression tumorale et la survie chez les souris portant le glioblastome humain intracr&acirc;nienne.

Glioblastoma &egrave; un tumore cerebrale fatale che diventa altamente vascolarizzato secernendo fattori proangiogenic e dipende dalla angiogenesi continua ad aumentare di dimensioni. Di conseguenza, una terapia antiangiogenetica successo dovrebbe fornire a lungo termine inibizione dell&#39;angiogenesi indotta da tumore, suggerendo a lungo termine del trasferimento del gene come una strategia terapeutica. In questo studio un recettore del fattore di crescita endoteliale vascolare solubile (sFlt-1) e un gene di fusione angiostatina endostatina (statina-AE) sono stati codelivered di glioblastoma umano xenotrapianti di trasferimento di geni virali utilizzando il transposon Sleeping Beauty (SB). In xenotrapianti impiantati sotto la cute, co-iniezione di entrambi hanno mostrato di transgeni contrassegnato attivit&agrave; antitumorale come dimostrato dalla riduzione della densit&agrave; di vasi tumorali, inibizione o abolizione della crescita del glioma e aumento della sopravvivenza degli animali (P = 0,003). Utilizzando engrafted gliomi intracranici luciferase-stabile, l&#39;effetto antitumorale di convezione-enhanced consegna del plasmide che DNA nel tumore &egrave; stato valutato dalla luciferasi in vivo imaging. Regressione tumorale sostenuta dei gliomi intracranici &egrave; stato raggiunto solo quando AE statina e sFlt-1 trasposoni sono stati somministrati con SB-ha-codifica del DNA per facilitare l&#39;espressione a lungo termine. Mostriamo che SB pu&ograve; essere usata per aumentare significativamente la sopravvivenza degli animali (P = 0,008) di trasferimento genico antiangiogenetica combinatoria in un modello di glioma intracranica.

Terapia genica antiangiogenetica combinatoria di trasferimento di geni virali utilizzando il sonno transposon bellezza provoca regressione tumorale e migliora la sopravvivenza nei topi cuscinetto intracranica glioblastoma umano.

Breast cancer patients with brain metastasis have a dismal prognosis. We determined the ability of immunostimulatory CpG oligodeoxynucleotides (ODN) to treat or prevent brain metastasis in a mouse model.

Effective CpG immunotherapy of breast carcinoma prevents but fails to eradicate established brain metastasis.

Patients atteints de cancer du sein avec m&eacute;tastases c&eacute;r&eacute;brales ont un pronostic sombre. Nous avons d&eacute;termin&eacute; la capacit&eacute; d&#39;immunostimulantes CpG oligodeoxynucleotides (ODN) pour traiter ou pr&eacute;venir les m&eacute;tastases c&eacute;r&eacute;brales dans un mod&egrave;le murin.

Efficace CpG immunoth&eacute;rapie du cancer du sein emp&ecirc;che mais ne parvient pas &agrave; &eacute;radiquer les m&eacute;tastases c&eacute;r&eacute;brales &eacute;tablies.

Pazienti affetti da cancro al seno con metastasi cerebrali hanno una prognosi lugubre. Abbiamo determinato la capacit&agrave; immunostimolante CpG oligodeoxynucleotides (ODN) per trattare o prevenire le metastasi cerebrali in un modello del mouse.

Article	Year
Combinatorial antiangiogenic gene therapy by nonviral gene transfer using the sleeping beauty transposon causes tumor regression and improves survival in mice bearing intracranial human glio... Molecular therapy : the journal of the American Society of Gene Therapy\| PubMed ID: 16150649	2005
Effective CpG immunotherapy of breast carcinoma prevents but fails to eradicate established brain metastasis. Clinical cancer research : an official journal of the American Association for Cancer Research\| PubMed ID: 18765540	2008

Isabelita Vengco

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