July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Infectious knockdown of CREB and HIF-1 for the treatment of metastatic uveal melanoma
Author Affiliations & Notes
  • Shahar Frenkel
    Ophthalmology, Hadassah-Hebrew Univ Med Ctr, Mevaseret Zion, Israel
  • Ana Voropaev
    Ophthalmology, Hadassah-Hebrew Univ Med Ctr, Mevaseret Zion, Israel
    Biochemistry and Molecular Biology, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
  • Maria Gimmelshein
    Ophthalmology, Hadassah-Hebrew Univ Med Ctr, Mevaseret Zion, Israel
    Biochemistry and Molecular Biology, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
  • Dudi Shneor
    Ophthalmology, Hadassah-Hebrew Univ Med Ctr, Mevaseret Zion, Israel
    Biochemistry and Molecular Biology, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
  • Alik Honigman
    Biochemistry and Molecular Biology, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
  • Footnotes
    Commercial Relationships   Shahar Frenkel, US Provisional Patent Application No. 15/442,960 (Submitted) combinatorial treatment of chemotherapy and ‎armed viruses targeting tumor.‎ (P); Ana Voropaev, None; Maria Gimmelshein, None; Dudi Shneor, US Provisional Patent Application No. 15/442,960 (Submitted) combinatorial treatment of chemotherapy and ‎armed viruses targeting tumor.‎ (P); Alik Honigman, US Provisional Patent Application No. 15/442,960 (Submitted) combinatorial treatment of chemotherapy and ‎armed viruses targeting tumor.‎ (P)
  • Footnotes
    Support  ISF - Israeli Science Foundation, MOST - Ministry of Science and Technology
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 734. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Shahar Frenkel, Ana Voropaev, Maria Gimmelshein, Dudi Shneor, Alik Honigman; Infectious knockdown of CREB and HIF-1 for the treatment of metastatic uveal melanoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):734.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Purpose : To date, there are no effective treatments for metastatic uveal melanoma. We have previously shown that knockdown of the hypoxia regulator gene CREB is effective against uveal melanoma in vitro. The purpose of this study is to test the effect of infectious knockdown of CREB and HIF-1 in vivo.

Methods : Uveal melanoma cells (Mel270) expressing luciferase and infected with a MuLV-based replication competent retroviral (RCR) vector expressing either vACE-CREB, vACE-HIF-1 or vACE-NT (non-target) as a control, were injected subcutaneously over the front shoulder of SCID mice (5 mice per treatment). Tumors were followed weekly via bioluminescence (IVIS, Life Science). After 5 weeks, tumors were excised and measured. Use of animals had been approved by the IACUC of the Hebrew University of Jerusalem, Israel and complied with the ARVO Statement for the Use of Animals in Ophthalmic and Visual Research.

Results : Tumors infected with the armed viruses that knock either CREB or HIF-1 show a flat growth curve as opposed to the steady fast growth of the control tumors (Fig. 1). At the end of the experiment, the mean weight of the tumors infected with an armed virus knocking down HIF-1 is only 42% of the mean tumor weight of the control tumors, and the mean weight of the tumors infected with an armed virus knocking down CREB is only 16% of the mean control tumor.

Conclusions : Infectious knockdown via armed viruses targeting the hypoxia regulators CREB and HIF-1 is effective against metastatic uveal melanoma in vivo.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Uveal melanoma cells (Mel270) expressing LUC and infected by armed viruses knocking down either CREB (vACE-CREB) or HIF-1 (vACE-HIF-1), or by the control virus (vACE-NT) were injected subcutaneously in SCID mice and followed weekly via bioluminescence to measure tumor growth. Knockdown of either CREB or HIF-1 abolished UM tumor growth in mice.

Uveal melanoma cells (Mel270) expressing LUC and infected by armed viruses knocking down either CREB (vACE-CREB) or HIF-1 (vACE-HIF-1), or by the control virus (vACE-NT) were injected subcutaneously in SCID mice and followed weekly via bioluminescence to measure tumor growth. Knockdown of either CREB or HIF-1 abolished UM tumor growth in mice.

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×