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An adenoviral vector expressing interleukin-4 modulates tumorigenicity and induces regression in a murine
C Addison1, J Gauldie, W Muller
1MCMASTER UNIV,DEPT BIOL,HAMILTON,ON L8S 4K1,CANADA. MCMASTER UNIV,DEPT PATHOL,HAMILTON,ON L8S 4K1,CANADA.
Abstract:
Anti-tumor activity of a recombinant adenovirus expressing murine IL-4 (AdCAIL-4) was investigated in a murine model of mammary adenocarcinoma. Primary tumor cells derived from mammary adenocarcinomas induced in transgenic mice by the middle T antigen gene of polyomavirus were infected with AdCAIL-4 and injected into syngeneic non-tumor bearing recipients. Expression of IL-4 by AdCAIL-4 transduced tumor cells significantly prolonged survival of all animals and prevented tumor development in 61% of recipient mice. When tumor bearing animals were injected intra-tumorally with AdCAIL-4, all animals survived at least 8 to 10 weeks longer than controls, and 50% of treated animals underwent complete tumor regression. Both en: vivo and in vivo treatment with AdCAIL-4 resulted in infiltration by eosinophils in and around the tumor site. Animals which had undergone complete tumor regression were protected from a second challenge suggesting that immunotherapy with Ad vectors expressing cytokines may protect from metastatic disease.
Insights
Recombinant adenovirus expressing interleukin-4 (AdCAIL-4) demonstrated significant anti-tumor activity in a murine model. This therapy prolonged survival, prevented tumor development, and induced complete regression in mammary adenocarcinoma.
Area of Science:
- Oncology
- Immunotherapy
- Gene Therapy
Background:
- Mammary adenocarcinoma is a prevalent cancer in mice.
- Interleukin-4 (IL-4) is a cytokine with immunomodulatory properties.
- Adenovirus vectors are effective tools for gene delivery.
Purpose of the Study:
- To investigate the anti-tumor activity of a recombinant adenovirus expressing murine IL-4 (AdCAIL-4).
- To evaluate the efficacy of AdCAIL-4 in a murine model of mammary adenocarcinoma.
Main Methods:
- Primary tumor cells from transgenic mice were infected with AdCAIL-4.
- Transduced cells were injected into syngeneic recipients.
- Tumor-bearing animals received intra-tumoral AdCAIL-4 injections.
Main Results:
- AdCAIL-4 expression prolonged survival and prevented tumor development in 61% of recipients.
- Intra-tumoral AdCAIL-4 treatment led to 50% complete tumor regression and extended survival by 8-10 weeks.
- Both in vitro and in vivo treatments resulted in eosinophil infiltration.
Conclusions:
- AdCAIL-4 exhibits significant anti-tumor efficacy in a murine mammary adenocarcinoma model.
- Immunotherapy with Ad vectors expressing cytokines shows potential for preventing metastatic disease.
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