Improved glioblastoma treatment with Ad5/35 fiber chimeric conditionally replicating adenoviruses

Hoffmann, Dennis; Meyer, Bernhard; Wildner, Oliver

doi:10.1002/jgm.1076

Cited by 39 publications

(30 citation statements)

References 79 publications

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“…65,66 Because different Ad serotypes have different cellular receptors, using different serotype or species (xenotype) fiber knobs or chimeric fibers can alter Ad tropism. 67 Examples include an Ad3 fiber knob (binds to CD80, CD86, and unknown receptor) and Ad5 fiber chimera (Ad5/3), which had greatly increased glioma infectivity and cytotoxicity in vitro 68,69 ; Ad5 with canine Ad1 (CK1) or porcine Ad (PK) fiber was more efficient than Ad5/3 70 ; and Ad16p (binds to CD46) and chimpanzee CV23 efficiently infected GSCs. 71 A screen of 16 Ad5 fiber chimeras on primary glioma cell cultures identified B-group viruses (Ad11, Ad35, Ad50 [bind to CD46, overexpressed in GBM]) as having greatly increased infectivity compared with Ad5, 72 with Ad5/35 extending survival in vivo.…”

Section: Adenovirusesmentioning

confidence: 99%

“…73 There are a number of promoters/enhancers that are active in glioma cells (glial fibrillary acidic protein (GFAP), nestin, midkine) or cancer cells generally (telomerase reverse transcriptase (TERT), survivin, vascular endothelial growth factor receptor (VEGFR)-1, E2F, Ki67), and these have been used to drive E1A expression in CRAds and found to selectively replicate in glioma cells. 60,68,74,75 Vaccinia virus VV is the vaccine agent used in the eradication of smallpox. This DNA virus has also demonstrated success as an oncolytic virus, with a rapid lytic replication cycle that occurs in the cytoplasm and ease of genetic manipulation that allows for the incorporation of therapeutic transgenes.…”

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confidence: 99%

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Current Status of Gene Therapy for Brain Tumors∗

Ning

Rabkin

2015

Translating Gene Therapy to the Clinic

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Glioblastoma (GBM) is the most common and deadliest primary brain tumor in adults, with current treatments having limited impact on disease progression. Therefore the development of alternative treatment options is greatly needed. Gene therapy is a treatment strategy that relies on the delivery of genetic material, usually transgenes or viruses, into cells for therapeutic purposes, and has been applied to GBM with increasing promise. We have included selectively replicationcompetent oncolytic viruses within this strategy, although the virus acts directly as a complex biologic anti-tumor agent rather than as a classic gene delivery vehicle. GBM is a good candidate for gene therapy because tumors remain locally within the brain and only rarely metastasize to other tissues; the majority of cells in the brain are post-mitotic, which allows for specific targeting of dividing tumor cells; and tumors can often be accessed neurosurgically for administration of therapy. Delivery vehicles used for brain tumors include nonreplicating viral vectors, normal adult stem/progenitor cells, and oncolytic viruses. The therapeutic transgenes or viruses are typically cytotoxic or express prodrug activating suicide genes to kill glioma cells, immunostimulatory to induce or amplify anti-tumor immune responses, and/or modify the tumor microenvironment such as blocking angiogenesis. This review describes current preclinical and clinical gene therapy strategies for the treatment of glioma.Treating malignant gliomas, of which glioblastoma (GBM) is the most common and least curable, remains a daunting challenge even after substantial efforts to develop alternative therapies. The current standard of care is maximal surgical resection followed by radiation and temozolomide chemotherapy; however, the median survival still remains less than 15 months. 1,2 This poor survival is due to the aggressive and invasive nature of the tumor cells, resistance to treatment, and the challenges of delivering therapeutics into the brain. 3 GBM is thought to be derived from a small population of glioblastoma stem cells (GSCs), so-called because of their stem cell-like properties of self-renewal and multilineage differentiation while being highly tumorigenic. [4][5][6] GSCs have become an important model for studying GBM because their xenografts mimic the heterogeneous histopathology of the patient's tumor from which they were derived 7,8 and they remain genotypically similar to the patient's tumor, in contrast to serum-cultured cell lines. 9 These cells have provided insights into the origin of tumor-initiating cells and new targets for therapy. Other GBM animal models include established glioma cell lines (human and rodent) implanted intracranially into immunodeficient or immunocompetent animals, and genetically engineered mice that spontaneously develop brain tumors or are induced with viral vectors. 10 GENE DELIVERY VEHICLES FOR GLIOBLASTOMAMost gene therapies for GBM use biologic vectors such as viruses or cells. Replicationdefective or non-repli...

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Section: Adenovirusesmentioning

confidence: 99%

mentioning

confidence: 99%

Current Status of Gene Therapy for Brain Tumors∗

Ning

Rabkin

2015

Translating Gene Therapy to the Clinic

View full text Add to dashboard Cite

show abstract

“…Moreover, a human α-fetoprotein (AFP) promoter has also been used in AFP-producing cells (9,10) and a cyclooxygenase-2 (Cox2) promoter (11,12) used in cells overexpressing Cox2. For high infection activity of adenovirus serotype 5 (Ad5), which requires the coxsackie and adenovirus receptor (CAR) localized on the surface of cancer cells, the Ad5/35 chimeric fiber was created (13,14). This chimeric fiber infected cells in a CD46-dependent mechanism.…”

Section: Introductionmentioning

confidence: 99%

An oncolytic adenovirus expressing interleukin-24 enhances antitumor activities in combination with paclitaxel in breast cancer cells

Lin

Qian

Bai

et al. 2013

Molecular Medicine Reports

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Abstract. Oncolytic adenoviruses are a novel class of anticancer treatment, based upon their ability to replicate selectively within malignant cells resulting in cell lysis. The replication-selective adenovirus, ZD55-IL-24, was constructed by harboring an E1B-55 kDa deletion and arming with interleukin-24 (IL-24). The microtubule-stabilizing drug paclitaxel (PTX) exhibits activity in relapsed cancer. In the present study, the synergistic antitumor effects of the combination of PTX and ZD55-IL-24 on breast cancer cells was investigated. The results demonstrated that there were different roles for PTX in the expression of transgenic mRNA and protein. ZD55-IL-24 combined with PTX induced marked growth inhibition of MDA-MB-231 and Bcap-37 cells. PTX increased viral uptake and appeared not to alter the replication of ZD55-IL-24 in breast cancer cells. Annexin V-fluorescein isothiocyanate/propidium iodide staining and the Hoechst 33258 assay indicated that ZD55-IL-24 induced an increase in the number of apoptotic cells when administered in combination with PTX. It was demonstrated that ZD55-IL-24 conjugated with PTX was highly concomitant, and increased proapoptotic proteins levels, activated caspase-3, -7 and -9 and downregulated anti-apoptotic proteins. These results suggested that ZD55-IL-24 in combination with PTX exhibited a markedly increased cytotoxic and apoptosis-inducing effect in breast cancer cells. Thus, this chemo-gene-viro therapeutic strategy was demonstrated to be superior to conventional chemotherapy or gene-viro therapy alone.

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“…Hoffmann D et al [55] used Ad5/35 fiber chimeric adenovirusses with vector binding redirected to the Ad35 receptor and replication under the control of the GFAP/Ki67 or E2F-1/COX-2 promoters. The native Ad5 was compared to the chimeric Ad5/35 fiber for their antineoplastic activity in a subcutaneous and intracranial glioblastoma xenograft model.…”

Section: Pseudotyped Adenovirusesmentioning

confidence: 99%

Targeting Adenoviral Entry to Enhance Oncolytic Antitumor Response

Haisma

Geerts²

2013

TOGTJ

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Conditionally replicative adenoviruses represent an innovative group of anticancer agents designed to destroy these cells by replication and lysis. A major problem associated with of the use of adenoviral vectors in gene therapy is its high liver uptake and lack of tumor selectivity upon systemic administration. To improve the efficacy of CRAds as anticancer agents, their infection efficiency on CAR-deficient tumor cells could be enhanced their by redirecting viral entry via a CAR-independent pathway. To redirect the entry pathway of adenoviruses and enhance their infectivity and specificity, two general strategies are being used. In the first strategy, the adenovirus genome is changed to alter the binding specificity of the viral capsid. In the second strategy, a two-component targeted adenovirus is created by binding of proteins with specific affinity for cancer cells onto the viral capsid. Despite effective targeting and tumor eradication in vitro and in mouse models, the results from systemic administration of targeted CrAds is limited. In addition, clinical effects of CrAds are disappointing up till now. Therefore, combination therapies in which targeted CrAds are combined with other types of therapy are being investigated.

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Improved glioblastoma treatment with Ad5/35 fiber chimeric conditionally replicating adenoviruses

Cited by 39 publications

References 79 publications

Current Status of Gene Therapy for Brain Tumors∗

Current Status of Gene Therapy for Brain Tumors∗

An oncolytic adenovirus expressing interleukin-24 enhances antitumor activities in combination with paclitaxel in breast cancer cells

Targeting Adenoviral Entry to Enhance Oncolytic Antitumor Response

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