Infectivity-Enhanced Cyclooxygenase-2-Based Conditionally Replicative Adenoviruses for Esophageal Adenocarcinoma Treatment

Davydova, Julia; Le, Long P.; Gavrikova, T. A.; Wang, Minghui; Krasnykh, Victor; Yamamoto, Masato

doi:10.1158/0008-5472.can-04-0064

Cited by 67 publications

(94 citation statements)

References 54 publications

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“…Likewise an Ad vector containing both an Ad3 knob and Ad3 shaft, 51 produced similar results on the cells tested (data not shown). These findings differ from those obtained in other studies which revealed considerable gene transfer augmentation via the Ad3 knob in the context of ovarian, [51][52][53] renal, 54 head and neck, 55 skin, 56 and gastrointestinal 20 cancers. Important to note also is the fact that these are epithelial-derived neoplasms (carcinomas) rather than mesenchymal (sarcomas).…”

Section: In Vivo Gene Transfercontrasting

confidence: 99%

“…[16][17][18] Indeed, such strategies yielded profound improvements in the oncolytic capability of CRAds relative to nonmodified vectors. 19,20 Recently, more radical modifications based on serotype and xenotype fiber-knob switching have been exploited to achieve enhanced transduction. [21][22][23] Furthermore, the ability to place large ligands onto the adenovirus fiber and protein IX by genetic means suggests the possibility of achieving truly retargeted CRAds.…”

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confidence: 99%

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An Imaging System to Monitor Efficacy of Adenovirus-Based Virotherapy Agents

Curiel¹

2006

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. (From -To) 1 Feb 04 -31 Jan 06 REPORT DATE (DD-MM-YYYY) February 2006 REPORT TYPE Final DATES COVERED TITLE AND SUBTITLEAn imaging system to monitor efficacy of adenovirus-based virotherapy agents PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBERThe University of Alabama at Birmingham Birmingham, AL 35294-0109 SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command Fort Detrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTOur preliminary data establish a number of important key points. Foremost, these results show that adenovirus can be genetically labeled with a fluorescent structural fusion protein through a complete replacement with IX-EGFP in a chimeric context. At least for our pIX-EGFP strategy, the label was incorporated into virions conferring a fluorescent property that allowed detection of individual particles. Ad-IX-EGFP binding and infection could both be detected via the fluorescent label. This capsid-labeling system is applicable to CRAds because it slightly decreased progeny yield but did not affect the cytopathic effect and spread of the virus. Notably, the level of pIX-EGFP fluorescence directly correlated with the amount of progeny production due to its dependence on E1 activity for expression. The data with pIX-EGFP fulfills all the requirements of the ideal monitoring system for CRAds except noninvasive detection which we propose to accomplish. Both our proposed capsid-labeling approaches demonstrate great promise for detection of viral replication and spread and hence monitoring of CRAds. To this end, we have conceptualized an approach to achieve direct biological labeling of adenoviruses for CRAd imaging. Specifically, we have identified a capsid protein of adenovirus, pIX, which allows genetic incorporation of heterologous peptides which are thereby presented on the surface of the virion. We have recently demonstrated that we can incorporate int...

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Section: In Vivo Gene Transfercontrasting

confidence: 99%

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confidence: 99%

An Imaging System to Monitor Efficacy of Adenovirus-Based Virotherapy Agents

Curiel¹

2006

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“…Intratumoral injection of OBP-405 for three consecutive days resulted in the significant inhibition of H1299-R5 tumor growth ( Figure 5) and selective spread of viruses throughout the tumor tissues (Figure 6b). Although the RGD fiber knob modification of selectively replicating adenoviruses, such as AdD24 containing the Rb-binding mutation in E1A (Lamfers et al, 2002) and the cyclooxygenase-2 (Cox-2) promoter-based adenovirus (Davydova et al, 2004), has been previously reported to reduce tumor size in vivo, the major advantage of OBP-405 is the broad applicability for many types of human cancers because of the telomerase-specific hTERT promoter. In fact, many studies have reported that telomerase is present in nearly all immortal cell lines and B90% of human tumors but seldom in normal somatic cells (Kim et al, 1994;Shay and Wright, 1996).…”

Section: Discussionmentioning

confidence: 99%

Enhanced oncolysis by a tropism-modified telomerase-specific replication-selective adenoviral agent OBP-405 (‘Telomelysin-RGD’)

et al. 2005

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Replication-competent oncolytic viruses are being developed for human cancer therapy. We previously reported that an attenuated adenovirus (OBP-301, 'Telomelysin'), in which the hTERT promoter element drives expression of E1A and E1B genes linked with an IRES, could replicate in cancer cells, and causes selective lysis of cancer cells. We further constructed OBP-405 ('Telomelysin-RGD') that contains an RGD motif in the HI loop of the fiber knob. We examined whether OBP-405 could be effective in overcoming the limitations of OBP-301, specifically their inefficient infection into cells lacking the primary receptor, the coxsackievirus and adenovirus receptor (CAR). By flow cytometric analysis, H1299 (lung) and SW620 (colorectal) tumor cells showed high levels of CAR expression, whereas LN444 (glioblastoma), LNZ308 (glioblastoma), and H1299-R5 (lung) tumor cells were negative for CAR expression. A quantitative realtime PCR analysis demonstrated that fiber-modified OBP-405 infected more efficiently than OBP-301, although the intracellular replication rate of both viruses was consistent. The comparative antitumor effect of fibermodified OBP-405 and unmodified OBP-301 for human cancer cells was evaluated in vitro by XTT assay as well as in vivo by using athymic mice carrying xenografts. OBP-405 had a profound oncolytic effect on human cancer cell lines compared to OBP-301, in particular on cells with low CAR expression. Intratumoral injection of 10 7 plaque-forming units of OBP-405 into CAR-negative H1299-R5 lung tumor xenografts in nu/nu mice resulted in a significant inhibition of tumor growth and long-term survival in all treated mice. Moreover, selective replication of OBP-405 in the distant, uninjected H1299-R5 tumors was demonstrated. Our results suggest that fiber-modified replication-competent adenovirus OBP-405 exhibits a broad target range by increasing infection efficiency, an outcome that has important implications for the treatment of human cancers.

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“…Oncolytic Adenoviruses Ad5.2xTyr 30 and Ad5/3.2xTyr 10 and nonreplication restricted adenoviruses Ad5wt and Ad5/3 35 were amplified in Colo829 cells. All viruses were purified by two rounds of cesium chloride equilibrium density gradient ultracentrifugation.…”

Section: Recombinant Adenovirusesmentioning

confidence: 99%

Modulation of viability and maturation of human monocyte‐derived dendritic cells by oncolytic adenoviruses

Schierer

Hesse

Müller

et al. 2007

Intl Journal of Cancer

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Adenoviral oncolysis is a promising new modality for treatment of cancer based on selective viral replication in tumor cells. However, tumor cell killing by adenoviral oncolysis needs to be improved to achieve therapeutic benefit in the clinic. Towards this end, the activation of anti-tumor immunity by adenoviral oncolysis might constitute a potent mechanism for systemic killing of uninfected tumor cells, thereby effectively complementing direct tumor cell killing by the virus. Knowledge of anti-tumor immune induction by adenoviral oncolysis, however, is lacking mostly due to species-specificity of adenovirus replication, which has hampered studies of human oncolytic adenoviruses in animals. We suggest the analysis of interactions of oncolytic adenoviruses with human immune cells as rational basis for the implementation of adenoviral oncolysis-induced anti-tumor immune activation. The goal of our study was to investigate how oncolytic adenoviruses affect human dendritic cells (DCs), key regulators of innate and adoptive immunity that are widely investigated as tumor vaccines. We report that melanoma-directed oncolytic adenoviruses, like replication-deficient adenoviruses but unlike adenoviruses with unrestricted replication potential, are not toxic to monocytederived immature DCs and do not block DC maturation by external stimuli. Of note, this is in contrast to reports for other viruses/ viral vectors and represents a prerequisite for anti-tumor immune activation by adenoviral oncolysis. Furthermore, we show that these oncolytic adenoviruses alone do not or only partially induce DC maturation. Thus additional signals are required for optimal immune activation. These could be delivered, for example, by inserting immunoregulatory transgenes into the oncolytic adenovirus genome. ' 2007 Wiley-Liss, Inc.Key words: oncolytic adenovirus; dendritic cell; DC maturation; virotherapy; tumor vaccination Oncolytic adenoviruses are emerging agents for the treatment of cancer based on tumor cell killing by virus infection, replication, cell lysis and spread. 1,2 Tumor-selectivity of virus replication is pivotal for this therapeutic strategy and has been achieved for oncolytic adenoviruses by (i) the mutation of adenoviral genes that are required for viral replication in normal cells, but which are dispensable in tumor cells, and (ii) the expression of essential viral genes, mostly of E1A, from heterologous, tumor-selective promoters. 1 Importantly, the advanced knowledge of the adenovirus structure, genome and replication cycle facilitates molecular modifications to the virus that are required or beneficial for therapeutic applications: besides the introduction of tumor-selective replication and cell killing potential, these are the modification of the virus tropism, or the expression of therapeutic genes. 3,4 Oncolytic adenoviruses have shown promise in clinical trials, which demonstrated proof-of-concept for tumor-selective virus replication and a favorable safety profile. 5,6 However, therapeutic efficacy of the investigat...

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Infectivity-Enhanced Cyclooxygenase-2-Based Conditionally Replicative Adenoviruses for Esophageal Adenocarcinoma Treatment

Cited by 67 publications

References 54 publications

An Imaging System to Monitor Efficacy of Adenovirus-Based Virotherapy Agents

An Imaging System to Monitor Efficacy of Adenovirus-Based Virotherapy Agents

Enhanced oncolysis by a tropism-modified telomerase-specific replication-selective adenoviral agent OBP-405 (‘Telomelysin-RGD’)

Modulation of viability and maturation of human monocyte‐derived dendritic cells by oncolytic adenoviruses

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