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Therapeutic Efficacy and Systemic Antitumor T Cell Immunity Induced by RheoSwitch-Regulated IL-12 Expression after Intratumoral Injection of Adenovirus Vector or Vector-Transduced Dendritic Cells

Authors
  • Chan, Tim
  • Lewis, Jonathan
  • Herberman, Ronald B.
Type
Book
Journal
Gene Therapy of Cancer
Publication Date
Jan 01, 2014
Pages
363–376
Identifiers
DOI: 10.1016/B978-0-12-394295-1.00025-1
ISBN: 978-0-12-394295-1
Source
Elsevier
Keywords
License
Unknown

Abstract

Interleukin-12 (IL-12) is a potent immunostimulatory cytokine that activates the innate and adaptive cellular immune system and has shown significant therapeutic activity in preclinical models, but severe toxicity of systemically administered IL-12 in cancer patients has limited clinical utilization. Direct delivery into the tumor, along with regulated gene expression, provides a process that may limit the toxic side effects due to high systemic levels of IL-12. Utilizing the RheoSwitch Therapeutic System® (RTS®) expression platform and an orally active activator ligand, intratumoral injections of dendritic cells transduced with adenovirus vector (Ad)-RTS-IL-12 or the Ad-RTS-IL-12 itself into the tumor have induced significant antitumor activity in mouse tumor models and are currently being assessed in clinical trials. The demonstration of RTS-IL-12 proof-of-principle provides a foundation for potential RTS-regulated expression of various therapeutic genes for a variety of cancers or other diseases, using a viral- or cellular-based approach to enhance treatment safety and therapeutic efficacy.

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