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Article: A Virus-Infected, Reprogrammed Somatic cell-derived Tumor cell (VIReST) vaccination regime can prevent initiation and progression of pancreatic cancer

TitleA Virus-Infected, Reprogrammed Somatic cell-derived Tumor cell (VIReST) vaccination regime can prevent initiation and progression of pancreatic cancer
Authors
Issue Date2020
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://clincancerres.aacrjournals.org/
Citation
Clinical Cancer Research, 2020, v. 26 n. 2, p. 465-476 How to Cite?
AbstractPurpose: Pancreatic cancer remains one of the most lethal cancers, and late detection renders most tumors refractory to conventional therapies. Development of cancer prophylaxis may be the most realistic option for improving mortality associated with this disease. Here, we develop a novel individualized prophylactic and therapeutic vaccination regimen using induced pluripotent stem cells (iPSC), gene editing, and tumor-targeted replicating oncolytic viruses. Experimental Design: We created a Virus-Infected, Reprogrammed Somatic cell-derived Tumor cell (VIReST) regime. iPSCs from healthy cells were induced to pancreatic tumor cells using in situ gene editing via stable provision of KRasG12D and p53R172H tumor driver mutations. These cells were preinfected with oncolytic Adenovirus (AdV) as prime or Vaccinia virus (VV) as boost, to improve vaccine immunogenicity, prior to delivery of vaccines in a sequential regime to young KPC transgenic mice, genetically programmed to develop pancreatic cancer, to prevent and delay disease development. Results: Tumor cells preinfected with oncolytic AdV as prime or VV as boost were the best regime to induce tumor-specific immunity. iPSC-derived tumor cells were highly related in antigen repertoire to pancreatic cancer cells of KPC transgenic mice, suggesting that an individual's stem cells can provide an antigenically matched whole tumor cell vaccine. The VIReST vaccination primed tumor-specific T-cell responses, resulting in delayed disease emergence and progression and significantly prolonged survival of KPC transgenic mice. Importantly, this regime was well-tolerated and nontoxic. Conclusions: These results provide both proof of concept and a robust technology platform for the development of personalized prophylactic cancer vaccines to prevent pancreatic malignancies in at-risk individuals.
Persistent Identifierhttp://hdl.handle.net/10722/290511
ISSN
2019 Impact Factor: 10.107
2015 SCImago Journal Rankings: 5.314
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLu, S-
dc.contributor.authorZhang, Z-
dc.contributor.authorDu, P-
dc.contributor.authorChard, LS-
dc.contributor.authorYan, W-
dc.contributor.authorEl-Khouri, M-
dc.contributor.authorWang, Z-
dc.contributor.authorZhang, Z-
dc.contributor.authorChu, Y-
dc.contributor.authorGao, D-
dc.contributor.authorZhang, Q-
dc.contributor.authorZhang, L-
dc.contributor.authorNagano, A-
dc.contributor.authorWang, J-
dc.contributor.authorChelala, C-
dc.contributor.authorLiu, J-
dc.contributor.authorChen, J-
dc.contributor.authorLiu, P-
dc.contributor.authorDong,, Y-
dc.contributor.authorWang, S-
dc.contributor.authorLi, X-
dc.contributor.authorDong, J-
dc.contributor.authorLemoine, NR-
dc.contributor.authorPei, D-
dc.contributor.authorWang, Y-
dc.date.accessioned2020-11-02T05:43:17Z-
dc.date.available2020-11-02T05:43:17Z-
dc.date.issued2020-
dc.identifier.citationClinical Cancer Research, 2020, v. 26 n. 2, p. 465-476-
dc.identifier.issn1078-0432-
dc.identifier.urihttp://hdl.handle.net/10722/290511-
dc.description.abstractPurpose: Pancreatic cancer remains one of the most lethal cancers, and late detection renders most tumors refractory to conventional therapies. Development of cancer prophylaxis may be the most realistic option for improving mortality associated with this disease. Here, we develop a novel individualized prophylactic and therapeutic vaccination regimen using induced pluripotent stem cells (iPSC), gene editing, and tumor-targeted replicating oncolytic viruses. Experimental Design: We created a Virus-Infected, Reprogrammed Somatic cell-derived Tumor cell (VIReST) regime. iPSCs from healthy cells were induced to pancreatic tumor cells using in situ gene editing via stable provision of KRasG12D and p53R172H tumor driver mutations. These cells were preinfected with oncolytic Adenovirus (AdV) as prime or Vaccinia virus (VV) as boost, to improve vaccine immunogenicity, prior to delivery of vaccines in a sequential regime to young KPC transgenic mice, genetically programmed to develop pancreatic cancer, to prevent and delay disease development. Results: Tumor cells preinfected with oncolytic AdV as prime or VV as boost were the best regime to induce tumor-specific immunity. iPSC-derived tumor cells were highly related in antigen repertoire to pancreatic cancer cells of KPC transgenic mice, suggesting that an individual's stem cells can provide an antigenically matched whole tumor cell vaccine. The VIReST vaccination primed tumor-specific T-cell responses, resulting in delayed disease emergence and progression and significantly prolonged survival of KPC transgenic mice. Importantly, this regime was well-tolerated and nontoxic. Conclusions: These results provide both proof of concept and a robust technology platform for the development of personalized prophylactic cancer vaccines to prevent pancreatic malignancies in at-risk individuals.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://clincancerres.aacrjournals.org/-
dc.relation.ispartofClinical Cancer Research-
dc.titleA Virus-Infected, Reprogrammed Somatic cell-derived Tumor cell (VIReST) vaccination regime can prevent initiation and progression of pancreatic cancer-
dc.typeArticle-
dc.identifier.emailLiu, P: pliu88@hku.hk-
dc.identifier.authorityLiu, P=rp02328-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/1078-0432.CCR-19-1395-
dc.identifier.pmid31767564-
dc.identifier.scopuseid_2-s2.0-85077930907-
dc.identifier.hkuros317870-
dc.identifier.volume26-
dc.identifier.issue2-
dc.identifier.spage465-
dc.identifier.epage476-
dc.identifier.isiWOS:000507311000017-
dc.publisher.placeUnited States-
dc.identifier.issnl1078-0432-

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