Successful Adenovirus-Mediated Wild-Type <i>p53</i> Gene Transfer in Patients With Bladder Cancer by Intravesical Vector Instillation

Kuball, Jürgen; Wen, Sijian; Leißner, Joachim; Atkins, Derek; Meinhardt, Patricia; Quijano, Erlinda; Engler, Heidrun; Hutchins, Beth; Maneval, Daniel C.; Grace, Michael J.; Fritz, Mary Ann; Störkel, Stefan; Thüroff, Joachim W.; Huber, Christoph; Schüler, Martin

doi:10.1200/jco.2002.20.4.957

Cited by 79 publications

(16 citation statements)

References 38 publications

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“…Vaccination against mutant P53 has been shown to be effective in tumor-bearing mice [150,151]. Several peptide vaccines and dendritic cell vaccines utilizing mutant P53-targeted immunotherapy are in clinical development [152][153][154][155]. A number of Phase I/II immunization trials have been conducted so far using P53 immunogens, but unfortunately none of them have shown acceptable clinical efficacy [156].…”

Section: Targeting Tp53 In Drug Developmentmentioning

confidence: 99%

Prognosis, Biology, and Targeting of TP53 Dysregulation in Multiple Myeloma

Flynt¹,

Bisht²,

Sridharan³

et al. 2020

Cells

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Multiple myeloma (MM) is the second most common hematological cancer and is characterized by genetic features including translocations, chromosomal copy number aberrations, and mutations in key oncogene and tumor suppressor genes. Dysregulation of the tumor suppressor TP53 is important in the pathogenesis of many cancers, including MM. In newly-diagnosed MM patients, TP53 dysregulation occurs in three subsets: monoallelic deletion as part of deletion of chromosome 17p (del17p) (~8%), monoallelic mutations (~6%), and biallelic inactivation (~4%). Del17p is an established high-risk feature in MM and is included in current disease staging criteria. Biallelic inactivation and mutation have also been reported in MM patients but are not yet included in disease staging criteria for high-risk disease. Emerging clinical and genomics data suggest that the biology of high-risk disease is complex, and so far, traditional drug development efforts to target dysregulated TP53 have not been successful. Here we review the TP53 dysregulation literature in cancer and in MM, including the three segments of TP53 dysregulation observed in MM patients. We propose a reverse translational approach to identify novel targets and disease drivers from TP53 dysregulated patients to address the unmet medical need in this setting.

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Section: Targeting Tp53 In Drug Developmentmentioning

confidence: 99%

Prognosis, Biology, and Targeting of TP53 Dysregulation in Multiple Myeloma

Flynt¹,

Bisht²,

Sridharan³

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…Of the 19 patients treated, 1 showed complete regression (5%), 11 demonstrated partial regression (58%), 3 showed stable disease (16%), 2 showed progressive disease (11%), and 2 were unevaluable (11%). In a bladder carcinoma trial, 12 patients received either intratumoral or intravesicular injections of rAd-p53 at doses of 7.5 ϫ 10 11 to 7.5 ϫ 10 13 VP (Kuball et al, 2002). Higher transduction efficiency was observed when using the intravesicular delivery method.…”

Section: Introductionmentioning

confidence: 99%

Current Status of Gendicine in China: Recombinant Human Ad-p53 Agent for Treatment of Cancers

Peng¹

2005

Human Gene Therapy

378

237

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“…Delivery of adenovirus carrying p53 with a transduction enhancing agent improved p53 gene delivery and protein expression was found in patient tissue samples (Kuball et al 2002). Though higher doses of the virus were administered, no dose toxicity was observed (Kuball et al 2002). Similarly no serious adverse effects were reported by Malmstrom et al from a recently concluded Phase I/IIa trial using AdCD40L (Malmstrom et al 2010).…”

Section: Gene Therapy Clinical Trialsmentioning

confidence: 96%

“…However, adenovirus therapy was safe and well tolerated (Pagliaro et al 2003). Delivery of adenovirus carrying p53 with a transduction enhancing agent improved p53 gene delivery and protein expression was found in patient tissue samples (Kuball et al 2002). Though higher doses of the virus were administered, no dose toxicity was observed (Kuball et al 2002).…”

Section: Gene Therapy Clinical Trialsmentioning

confidence: 99%