Infectivity-Enhanced, Conditionally Replicative Adenovirus for COX-2-Expressing Castration-Resistant Prostate Cancer

Tatyana Gavrikova; Naohiko Nakamura; Julia Davydova; Emmanuel S. Antonarakis; Masato Yamamoto

doi:10.3390/v15040901

Infectivity-Enhanced, Conditionally Replicative Adenovirus for COX-2-Expressing Castration-Resistant Prostate Cancer

Tatyana Gavrikova, Naohiko Nakamura, Julia Davydova, Emmanuel S. Antonarakis, Masato Yamamoto

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Background: The development of conditionally replicative adenoviruses (CRAds) for castration-resistant prostate cancer (CRPC), particularly neuroendocrine prostate cancer (NEPC), has two major obstacles: choice of control element and poor infectivity. We applied fiber-modification-based infectivity enhancement and an androgen-independent promoter (cyclooxynegase-2, COX-2) to overcome these issues. Methods: The properties of the COX-2 promoter and the effect of fiber modification were tested in two CRPC cell lines (Du-145 and PC3). Fiber-modified COX-2 CRAds were tested in vitro for cytocidal effect as well as in vivo for antitumor effect with subcutaneous CRPC xenografts. Results: In both CRPC cell lines, the COX-2 promoter showed high activity, and Ad5/Ad3 fiber modification significantly enhanced adenoviral infectivity. COX-2 CRAds showed a potent cytocidal effect in CRPC cells with remarkable augmentation by fiber modification. In vivo, COX-2 CRAds showed an antitumor effect in Du-145 while only Ad5/Ad3 CRAd showed the strongest antitumor effect in PC3. Conclusion: COX-2 promoter–based, infectivity-enhanced CRAds showed a potent antitumor effect in CRPC/NEPC cells.

Original language	English (US)
Article number	901
Journal	Viruses
Volume	15
Issue number	4
DOIs	https://doi.org/10.3390/v15040901
State	Published - Apr 2023

Bibliographical note

Publisher Copyright:
© 2023 by the authors.

Keywords

NEPC
adenoviral
castration resistant
cyclooxygenase
neuroendocrinal prostate cancer
prostate cancer
replicative
virotherapy

PubMed: MeSH publication types

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Infectivity-Enhanced, Conditionally Replicative Adenovirus for COX-2-Expressing Castration-Resistant Prostate Cancer",

abstract = "Background: The development of conditionally replicative adenoviruses (CRAds) for castration-resistant prostate cancer (CRPC), particularly neuroendocrine prostate cancer (NEPC), has two major obstacles: choice of control element and poor infectivity. We applied fiber-modification-based infectivity enhancement and an androgen-independent promoter (cyclooxynegase-2, COX-2) to overcome these issues. Methods: The properties of the COX-2 promoter and the effect of fiber modification were tested in two CRPC cell lines (Du-145 and PC3). Fiber-modified COX-2 CRAds were tested in vitro for cytocidal effect as well as in vivo for antitumor effect with subcutaneous CRPC xenografts. Results: In both CRPC cell lines, the COX-2 promoter showed high activity, and Ad5/Ad3 fiber modification significantly enhanced adenoviral infectivity. COX-2 CRAds showed a potent cytocidal effect in CRPC cells with remarkable augmentation by fiber modification. In vivo, COX-2 CRAds showed an antitumor effect in Du-145 while only Ad5/Ad3 CRAd showed the strongest antitumor effect in PC3. Conclusion: COX-2 promoter–based, infectivity-enhanced CRAds showed a potent antitumor effect in CRPC/NEPC cells.",

keywords = "NEPC, adenoviral, castration resistant, cyclooxygenase, neuroendocrinal prostate cancer, prostate cancer, replicative, virotherapy",

author = "Tatyana Gavrikova and Naohiko Nakamura and Julia Davydova and Antonarakis, {Emmanuel S.} and Masato Yamamoto",

note = "Publisher Copyright: {\textcopyright} 2023 by the authors.",

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doi = "10.3390/v15040901",

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volume = "15",

journal = "Viruses",

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AU - Nakamura, Naohiko

AU - Davydova, Julia

AU - Antonarakis, Emmanuel S.

AU - Yamamoto, Masato

PY - 2023/4

Y1 - 2023/4

N2 - Background: The development of conditionally replicative adenoviruses (CRAds) for castration-resistant prostate cancer (CRPC), particularly neuroendocrine prostate cancer (NEPC), has two major obstacles: choice of control element and poor infectivity. We applied fiber-modification-based infectivity enhancement and an androgen-independent promoter (cyclooxynegase-2, COX-2) to overcome these issues. Methods: The properties of the COX-2 promoter and the effect of fiber modification were tested in two CRPC cell lines (Du-145 and PC3). Fiber-modified COX-2 CRAds were tested in vitro for cytocidal effect as well as in vivo for antitumor effect with subcutaneous CRPC xenografts. Results: In both CRPC cell lines, the COX-2 promoter showed high activity, and Ad5/Ad3 fiber modification significantly enhanced adenoviral infectivity. COX-2 CRAds showed a potent cytocidal effect in CRPC cells with remarkable augmentation by fiber modification. In vivo, COX-2 CRAds showed an antitumor effect in Du-145 while only Ad5/Ad3 CRAd showed the strongest antitumor effect in PC3. Conclusion: COX-2 promoter–based, infectivity-enhanced CRAds showed a potent antitumor effect in CRPC/NEPC cells.

AB - Background: The development of conditionally replicative adenoviruses (CRAds) for castration-resistant prostate cancer (CRPC), particularly neuroendocrine prostate cancer (NEPC), has two major obstacles: choice of control element and poor infectivity. We applied fiber-modification-based infectivity enhancement and an androgen-independent promoter (cyclooxynegase-2, COX-2) to overcome these issues. Methods: The properties of the COX-2 promoter and the effect of fiber modification were tested in two CRPC cell lines (Du-145 and PC3). Fiber-modified COX-2 CRAds were tested in vitro for cytocidal effect as well as in vivo for antitumor effect with subcutaneous CRPC xenografts. Results: In both CRPC cell lines, the COX-2 promoter showed high activity, and Ad5/Ad3 fiber modification significantly enhanced adenoviral infectivity. COX-2 CRAds showed a potent cytocidal effect in CRPC cells with remarkable augmentation by fiber modification. In vivo, COX-2 CRAds showed an antitumor effect in Du-145 while only Ad5/Ad3 CRAd showed the strongest antitumor effect in PC3. Conclusion: COX-2 promoter–based, infectivity-enhanced CRAds showed a potent antitumor effect in CRPC/NEPC cells.

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KW - virotherapy

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Infectivity-Enhanced, Conditionally Replicative Adenovirus for COX-2-Expressing Castration-Resistant Prostate Cancer

Abstract

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