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Updated: Jun 25, 2026
Virus Delivery of CRISPR Guides to the Murine Prostate for Gene Alteration
Published on: April 27, 2018
Replication-competent Ad11p vector (RCAd11p) efficiently transduces and replicates in hormone-refractory metastatic
Linda Sandberg1, Praveen Papareddy, Jim Silver
1Department of Virology, Umeå University, SE-901 85 Umeå, Sweden.
Abstract:
Selective replication-competent adenovirus serotype 5 vectors have been used for prostate cancer therapy. Unfortunately, gene transfer is inefficient because hormone-refractory metastatic prostate cancer cells have minimal coxsackievirus-adenovirus receptor expression. Vectors based on species B adenoviruses are attractive tools for use in human gene therapy because the viruses have low seroprevalence and they have efficient transduction capacity. Most species B adenoviruses use ubiquitously expressed complement-regulatory CD46 protein as a cellular receptor. Here we report the transduction efficacy and oncolytic capacity of a replication-competent Ad11p (RCAd11p) vector in human prostate cancer cells. Green fluorescent protein was efficiently expressed in a dose-dependent manner in PC-3 and DU 145 cells derived from metastasis of prostate cancer to bone and brain, respectively. However, transduction was less effective in LNCaP cells derived from prostate cancer metastasis to lymph nodes. The oncolytic capacity of the RCAd11p vector was 100 times higher in PC-3 cells than in the two other cell lines. The oncolysis was independent of the level of expression of p53 in the cells or on the absence of E1B55k expression in the vector. In vivo experiments revealed significant growth inhibition of PC-3 tumors in the xenograft mouse group treated with RCAd11p vector or Ad11pwt in comparison with the untreated control group. Thus, we have demonstrated that RCAd11p vector intrinsically possesses oncolytic properties, which were active in targeting tumor cells. Consequently, the novel RCAd11p vector has great potential for the treatment of incurable metastatic prostate disease.
Insights
A novel replication-competent adenovirus serotype 11p (RCAd11p) vector shows promise for prostate cancer therapy. This vector efficiently targets and destroys prostate cancer cells, offering potential for treating metastatic disease.
Area of Science:
- Oncolytic virotherapy
- Gene therapy
- Adenovirus vectors
Background:
- Adenovirus serotype 5 vectors are limited for prostate cancer gene therapy due to low coxsackievirus-adenovirus receptor expression on hormone-refractory cells.
- Species B adenoviruses offer advantages, including low human seroprevalence and efficient transduction via the CD46 receptor.
Purpose of the Study:
- To evaluate the transduction efficacy and oncolytic capacity of a replication-competent Ad11p (RCAd11p) vector in human prostate cancer cells.
- To assess the potential of RCAd11p as a therapeutic agent for metastatic prostate cancer.
Main Methods:
- Transduction efficacy was assessed by green fluorescent protein expression in PC-3, DU 145, and LNCaP prostate cancer cell lines.
- Oncolytic capacity was measured by comparing cell killing in different cell lines.
- In vivo efficacy was evaluated in PC-3 tumor xenografts in mice.
Main Results:
- RCAd11p efficiently transduced PC-3 and DU 145 cells, with dose-dependent green fluorescent protein expression.
- Transduction was less effective in LNCaP cells.
- Oncolytic capacity was significantly higher (100-fold) in PC-3 cells compared to DU 145 and LNCaP cells.
- Oncolysis was independent of cellular p53 levels or vector E1B55k expression.
- In vivo, RCAd11p treatment significantly inhibited PC-3 tumor growth in mice.
Conclusions:
- The RCAd11p vector possesses intrinsic oncolytic properties and effectively targets prostate tumor cells.
- This novel vector demonstrates significant potential for the treatment of metastatic prostate cancer.
