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Retargeting to EGFR enhances adenovirus infection efficiency of squamous cell carcinoma
J L Blackwell1, C R Miller, J T Douglas
1Department of Medicine, University of Alabama at Birmingham, 35294, USA.
Background:
Adenovirus-mediated gene therapy has been used for squamous cell carcinoma of the head and neck (SCCHN), but the in vivo efficacy has been limited by a lack of tissue specificity and low infection efficiency. We are interested in improving cancer gene therapy strategies using targeted adenovirus vectors.
Objective:
To determine if the infection efficiency of adenovirus-mediated gene transfer to SCCHN cells could be enhanced by retargeting to the epidermal growth factor receptor (EGFR), which is known to be overexpressed in these tumors.
Design:
Epidermal growth factor receptor retargeting in SCCHN cells was accomplished with a bispecific antibody that recognized the knob domain of adenovirus as well as EGFR. Using this retargeting schema, we compared the infection efficiency and specificity of unmodified and EGFR-retargeted adenovirus.
Results:
Squamous cell carcinoma of the head and neck cell lines were shown to be infected by adenovirus with low efficiency, which is likely because of the low level of adenovirus receptor expressed in the SCCHN cells. Epidermal growth factor receptor retargeting markedly enhanced transduction in both SCCHN cell lines and primary tumor tissue, as indicated by the elevated levels of reporter gene expression. Furthermore, retargeting enhanced infection of tumor tissue compared with normal tissue from the same patient.
Conclusions:
Epidermal growth factor receptor retargeting enhanced adenovirus infection of SCCHN cells and, in doing so, augments the potency of the vector. This modification makes the vector potentially more valuable in the clinical setting.
Insights
Targeting epidermal growth factor receptors (EGFR) with adenovirus vectors significantly improves gene transfer efficiency in head and neck squamous cell carcinoma (SCCHN). This EGFR retargeting enhances cancer gene therapy, making it more potent for clinical applications.
Area of Science:
- Oncolytic virology
- Molecular and Cellular Oncology
- Gene Therapy
Background:
- Adenovirus-mediated gene therapy for head and neck squamous cell carcinoma (SCCHN) faces limitations in tissue specificity and infection efficiency.
- Improving targeted adenovirus vectors is crucial for effective cancer gene therapy strategies.
Purpose of the Study:
- To enhance adenovirus infection efficiency in SCCHN cells by retargeting to the epidermal growth factor receptor (EGFR).
- EGFR is overexpressed in SCCHN tumors, making it a promising target for retargeting.
Main Methods:
- Utilized a bispecific antibody to retarget adenovirus to EGFR on SCCHN cells.
- Compared infection efficiency and specificity of unmodified versus EGFR-retargeted adenovirus vectors.
Main Results:
- Adenovirus infection efficiency was low in SCCHN cells due to limited adenovirus receptor expression.
- EGFR retargeting significantly increased reporter gene expression in SCCHN cell lines and primary tumor tissue.
- Retargeting demonstrated enhanced infection of tumor tissue compared to normal tissue from the same patient.
Conclusions:
- EGFR retargeting substantially improves adenovirus infection of SCCHN cells.
- This enhancement increases the potency of adenovirus vectors for gene therapy.
- The modified vector shows increased potential for clinical applications in SCCHN treatment.