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Tumor-specific targeting with modified Sindbis viral vectors: evaluation with optical imaging and positron emission
Lars Stelter1, Jen-Chieh Tseng, Armen Torosjan
1Nuclear Medicine Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, USA. lars.stelter@charite.de
Purpose:
Sindbis virus (SINV) infect tumor cells specifically and systemically throughout the body. Sindbis vectors are capable of expressing high levels of transduced suicide genes and thus efficiently produce enzymes for prodrug conversion in infected tumor cells. The ability to monitor suicide gene expression levels and viral load in patients, after administration of the vectors, would significantly enhance this tumor-specific therapeutic option.
Procedures:
The tumor specificity of SINV is mediated by the 67-kDa laminin receptor (LR). We probed different cancer cell lines for their LR expression and, to determine the specific role of LR-expression in the infection cycle, used different molecular imaging strategies, such as bioluminescence, fluorescence molecular tomography, and positron emission tomography, to evaluate SINV-mediated infection in vitro and in vivo.
Results:
All cancer cell lines showed a marked expression of LR. The infection rates of the SINV particles, however, differed significantly among the cell lines.
Conclusion:
We used novel molecular imaging techniques to visualize vector delivery to different neoplatic cells. SINV infection rates proofed to be not solely dependent on cellular LR expression. Further studies need to evaluate the herein discussed ways of cellular infection and viral replication.
Insights
Sindbis virus (SINV) shows promise for cancer therapy by targeting tumor cells. However, infection rates vary, indicating factors beyond laminin receptor expression influence efficacy.
Area of Science:
- Oncolytic virotherapy
- Molecular imaging
- Cancer biology
Background:
- Sindbis virus (SINV) vectors offer targeted delivery of suicide genes to tumor cells for cancer therapy.
- Monitoring viral load and gene expression is crucial for enhancing SINV-based treatments.
Purpose of the Study:
- To investigate the role of the 67-kDa laminin receptor (LR) in Sindbis virus tumor cell specificity.
- To evaluate SINV infection rates in various cancer cell lines using molecular imaging techniques.
Main Methods:
- Assessed LR expression across different cancer cell lines.
- Employed bioluminescence, fluorescence molecular tomography, and positron emission tomography for in vitro and in vivo imaging.
- Quantified SINV infection rates in relation to LR expression.
Main Results:
- All tested cancer cell lines demonstrated significant LR expression.
- SINV infection rates varied considerably among cell lines, independent of LR levels.
Conclusions:
- Molecular imaging confirmed vector delivery to neoplastic cells.
- Cellular LR expression alone does not solely determine SINV infection rates.
- Further research is needed to elucidate mechanisms of SINV cellular infection and replication.
