Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer

Kaufman, Howard L.; Kim‐Schulze, Seunghee; Manson, Kelledy; DeRaffele, Gail; Mitcham, Josephine; Seo, Kang Seok; Kim, Dae Won; Marshall, John L.

doi:10.1186/1479-5876-5-60

Cited by 102 publications

(57 citation statements)

References 40 publications

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“…Although this treatment resulted in an MST of 6.3 months (1.5-21.1 months), the five patients who showed T cell responses achieved a longer survival period than the five patients who did not (15.1 and 3.9 months, respectively; P = 0.002) [38]. It should be noted that GM-CSF was used as a vaccine adjuvant in the latter trial (Table 2).…”

Section: Fowlpox Viral Vaccinementioning

confidence: 90%

Trials of vaccines for pancreatic ductal adenocarcinoma: Is there any hope of an improved prognosis?

et al. 2015

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Pancreatic tumors are chemoresistant and malignant, and there are very few therapeutic options for pancreatic cancer, as the disease is normally diagnosed at an advanced stage. Although attempts have been made to develop vaccine therapies for pancreatic cancer for a couple of decades, none of the resultant protocols or regimens have succeeded in improving the clinical outcomes of patients. We herein review vaccines tested within the past few years, including peptide, biological and multiple vaccines, and describe the three sets of criteria used to evaluate the therapeutic activity of vaccines in solid tumors.

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Section: Fowlpox Viral Vaccinementioning

confidence: 90%

Trials of vaccines for pancreatic ductal adenocarcinoma: Is there any hope of an improved prognosis?

et al. 2015

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“…The viral transfer of CEA and B7.1 into T cells was tested in a phase I trial but the results were not spectacular with only 3 out of 12 stable disease [65]. More promising results have been reported when several tumor-directing antigens, including CEA, together with co-stimulatory molecules were delivered to T cells with poxviruses since the overall survival was significantly increased in the patient demonstrating efficient immunization [66]. Providing the tumor environment with cytokines such as IL-12, or TNF-α did not result in regression of the tumors [67,68].…”

Section: Clinical Trials Completed and Ongoingmentioning

confidence: 93%

Gene Therapy of Pancreatic Cancer

Dabernat¹,

Lafitte²,

Bedel³

et al. 2013

J Genet Syndr Gene Ther

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Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors with a 5-year survival rate of less than 5%. The poor prognosis of the disease is associated with late diagnosis and a high degree of drug resistance has not been overcome during the past decades. Gemcitabine-based regimens are the first line therapy for advanced pancreatic cancer but are not curative. Recent new combination chemotherapies achieved significant benefits but toxicity makes their use controversial. Novel approaches are currently being developed; in particular cancer gene therapies are undergoing preclinical and clinical validation and are the topic of the present review. We will present different ways to design gene therapy against pancreatic cancers that have been validated in preclinical studies. We also reviewed the clinical trials already published or still ongoing.Citation: Dabernat S, Lafitte M, Bedel A, de Verneuil H, Moreau-Gaudry F (2013) Gene Therapy of Pancreatic Cancer. J Genet Syndr Gene Ther 4: 138. doi:10.4172/2157-7412.1000138 Page 2 of 6Volume 4 • Issue 4 • 1000138 Suicide Gene Therapy of Cancer J Genet Syndr Gene Ther ISSN: 2157-7412 JGSGT, an open access journal gene restoration efficiency [12]. Restoring a wild type SMAD4 did not always block tumor cells [13] rendering the use of this tumor suppressor controversial [14]. Many oncogenes can be deregulated and/or mutated in pancreatic cancers. Among them, mutations in the KRAS oncogene occur in almost all pancreatic adenorcinomas [9]. Thus, it is tempting to use direct anti-KRAS strategies to inhibit tumor growth (Figure 1b), since disappointing results have been obtained with inhibition of farnesyl transferases [1]. RNAi directed against mutated KRAS showed anti-tumor activity [15], limited the aggressive phenotype of the tumor cells [16] and potentiated gemcitabine antitumor activity [17]. Preclinical studies showed encouraging results with viral delivery systems such as oncolytic adenovirus [18]. However, this strategy has not been further tested in phase I clinical trials.In fact, pancreatic adenocarcinomas present very complex genetic alterations profiles. The Pancreatic Cancer Genome project has analyzed 23,219 transcripts and identified an average of 63 somatic mutations per PDAC affecting 12 core signaling pathways and the overexpression of 500 different genes in 24 tumors [19]. These highly versatile and unpredictable molecular patterns can explain the failure of single gene/pathway targeted adjuvant therapies. It is now critical to test therapies targeting several pathways or therapies that induce specific tumor cell death. Delivering a Suicide GeneWith the suicide gene approach, a gene that encodes a protein triggering tumor cell death is delivered to the tumor cells ( Figure 1c). The expression of the therapeutic gene can directly kill the cells (diphtheria toxin, [20]), or can render the cells sensitive to certain otherwise non toxic prodrugs (Gene Directed Enzyme Prodrug Therapy, GDEPT,[21]), or based on gemcitabine association ...

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“…Antibodies to vaccinia were seen in all ten patients and fi ve of eight evaluable patients developed antigenspecifi c T-cell responses. Median overall survival was 6.3 months and signifi cant prolonged survival was seen in patients who developed anti-CEA and anti-MUC1 immune responses (15.1 months versus 3.9 months) [ 76 ].…”

Section: Recombinant Vaccinesmentioning

confidence: 99%