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Evaluation of monocytes as carriers for armed oncolytic adenoviruses in murine and Syrian hamster models of cancer. | LitMetric

AI Article Synopsis

  • - The study investigates using replication-competent adenoviruses (OAV) as gene delivery vectors to enhance cancer treatment, aiming to prolong antitumor effects beyond just killing cancer cells.
  • - Monocytes, specifically human and hamster cell lines, were tested as carriers for OAVs, revealing that intratumoral delivery in hamsters allowed for repeated therapeutic cycles while reducing neutralizing antibodies that typically limit effectiveness.
  • - Utilizing monocytes loaded with a modified OAV that expresses interleukin-12 led to significant tumor reduction in hamsters, showcasing the potential for this method in improving cancer treatment outcomes.

Article Abstract

Replication-competent (oncolytic) adenoviruses (OAV) can be adapted as vectors for the delivery of therapeutic genes, with the aim of extending the antitumor effect beyond direct cytolysis. Transgene expression using these vectors is usually intense but short-lived, and repeated administrations are hampered by the rapid appearance of neutralizing antibodies (NAbs). We have studied the performance of monocytes as cell carriers to improve transgene expression in cancer models established in athymic mice and immunocompetent Syrian hamsters. Human and hamster monocytic cell lines (MonoMac6 and HM-1, respectively) were loaded with replication-competent adenovirus-expressing luciferase. Intravenous administration of these cells caused a modest increase in transgene expression in tumor xenografts, but this effect was virtually lost in hamsters. In contrast, intratumoral administration of HM-1 cells allowed repeated cycles of expression and achieved partial protection from NAbs in preimmunized hamsters bearing pancreatic tumors. To explore the therapeutic potential of this approach, HM-1 cells were loaded with a hypoxia-inducible OAV expressing the immunostimulatory cytokine interleukin-12 (IL-12). Three cycles of treatment achieved a significant antitumor effect in the hamster model, and transgene expression was detected following each administration, in contrast with the rapid neutralization of the free virus. We propose monocytes as carriers for multiple intratumoral administrations of armed OAVs.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3523252PMC
http://dx.doi.org/10.1089/hum.2012.043DOI Listing

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