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Utilizing the Antigen Capsid-Incorporation Strategy for the Development of Adenovirus Serotype 5-Vectored Vaccine Approaches
Published on: May 6, 2015
Chapter two--Adenovirus strategies for tissue-specific targeting
Matthew S Beatty1, David T Curiel
1Division of Cancer Biology, Department of Radiation Oncology, Washington University School of Medicine in St Louis, St Louis, Missouri, USA.
Abstract:
Cancer gene therapy approaches have benefited greatly from the utilization of molecular-based therapeutics. Of these, adenovirus-based interventions hold much promise as a platform for targeted therapeutic delivery to tumors. However, a barrier to this progression is the lack of native adenovirus receptor expression on a variety of cancer types. As such, any adenovirus-based cancer therapy must take into consideration retargeting the vector to nonnative cellular surface receptors. Predicated upon the knowledge gained in native adenovirus biology, several strategies to transductionally retarget adenovirus have emerged. Herein, we describe the biological hurdles as well as strategies utilized in adenovirus transductional targeting, covering the progress of both adapter-based and genetic manipulation-based targeting. Additionally, we discuss recent translation of these targeting strategies into a clinical setting.
Insights
Adenovirus gene therapy for cancer shows promise but requires retargeting vectors to cancer cells lacking native receptors. Strategies include adapter-based and genetic modifications for improved tumor targeting and clinical application.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Adenovirus vectors are promising for cancer gene therapy due to their therapeutic delivery capabilities.
- A significant challenge is the limited expression of native adenovirus receptors on many cancer cell types, hindering effective targeting.
- Overcoming this requires strategies to retarget adenovirus to non-native cellular surface receptors.
Purpose of the Study:
- To review biological hurdles and strategies for retargeting adenovirus vectors for cancer gene therapy.
- To cover advancements in both adapter-based and genetic manipulation-based targeting approaches.
- To discuss the clinical translation of these adenovirus targeting strategies.
Main Methods:
- Review of existing literature on adenovirus biology and targeting strategies.
- Analysis of adapter-based methods for redirecting adenovirus to alternative receptors.
- Examination of genetic engineering techniques to modify adenovirus for enhanced cancer cell recognition.
Main Results:
- Several strategies have been developed to overcome the lack of native adenovirus receptors on cancer cells.
- Adapter-based and genetic manipulation methods show progress in retargeting adenovirus vectors.
- These targeting strategies are increasingly being translated into clinical settings.
Conclusions:
- Retargeting adenovirus vectors is crucial for effective cancer gene therapy when native receptors are absent.
- Both adapter-based and genetic approaches offer viable solutions for enhancing adenovirus tumor targeting.
- The clinical application of these advanced adenovirus targeting strategies is advancing.
