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Localized interleukinâ12 delivery for immunotherapy of solid tumours
- Source :
- Journal of Cellular and Molecular Medicine
- Publication Year :
- 2013
- Publisher :
- Wiley, 2013.
-
Abstract
- Interleukin (IL)-12 is the key cytokine in the initiation of a Th1 response and has shown promise as an anti-cancer agent; however, clinical trials involving IL-12 have been unsuccessful due to toxic side-effects. To address this issue, lentiviral vectors were used to transduce tumour cell lines that were injected as an autologous tumour cell vaccine. The focus of the current study was to test the efficacy of this approach in a solid tumour model. SCCVII cells that were transduced to produce IL-12 at different concentrations were then isolated. Subcutaneous injection of parental SCCVII cells results in tumour development, while a mixture of IL-12-producing and non-producing cells results in tumour clearance. Interestingly, when comparing mice injected a mixture of SCCVII and either high IL-12-producing tumour cells or low IL-12-producing tumour cells, we observed that mixtures containing small amounts of high producing cells lead to tumour clearance, whereas mixtures containing large amounts of low producing cells fail to elicit protection, despite the production of equal amounts of total IL-12 in both mixtures. Furthermore, immunizing mice with IL-12-producing cells leads to the establishment of both local and systemic immunity against challenge with SCCVII. Using depletion antibodies, it was shown that both CD4(+) and CD8(+) cells are crucial for therapy. Lastly, we have established cell clones of other solid tumour cell lines (RM-1, LLC1 and moto1.1) that produce IL-12. Our results show that the delivery of IL-12 by cancer cells is an effective route for immune activation.
- Subjects :
- CD4-Positive T-Lymphocytes
Male
Genetic enhancement
medicine.medical_treatment
CD8-Positive T-Lymphocytes
Biology
Cancer Vaccines
Mice
lentivirus
Cell Line, Tumor
medicine
Animals
Mice, Inbred C3H
Interleukin
Original Articles
Cell Biology
Immunotherapy
Interleukin-12
gene therapy
Mice, Inbred C57BL
Cytokine
Head and Neck Neoplasms
Cell culture
Immunology
Cancer cell
Carcinoma, Squamous Cell
solid tumour
Interleukin 12
Cancer research
Molecular Medicine
Female
immunotherapy
Immunologic Memory
Neoplasm Transplantation
CD8
Subjects
Details
- ISSN :
- 15824934 and 15821838
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular and Molecular Medicine
- Accession number :
- edsair.doi.dedup.....0bb29a5d08269e5ee5a708595d5f7dc5