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- Title
Complete tumour regressions induced by vaccination with IL-12 gene-transduced tumour cells in combination with IL-15 in a melanoma model in mice.
- Authors
Lasek, Witold; Basak, Grzegorz; Şwitaj, Tomasz; Jakubowska, Anna B.; Wysocki, Piotr J.; Mackiewicz, Andrzej; Drela, Nadzieja; Jalili, Ahmad; Kamiński, Rafal; Kozar, Katarzyna; Jakóbisiak, Marek
- Abstract
In the present study, IL-12 gene-transduced B78-H1 melanoma cells (B78/IL-12) were used in combination with IL-15 to treat melanoma-bearing mice. Genetically modified B78/IL-12 cells, when injected subcutaneously, induced strong activation of antitumour mechanisms resulting in complete loss of tumourigenicity. In a therapeutic model, intratumoural injection of irradiated B78/IL-12 cells significantly delayed tumour growth and led to the regression of melanoma in one case. Similarly, consecutive daily injections of IL-15 markedly inhibited tumour progression with occasional curative effects. When used in combination, vaccination with B78/IL-12 cells and treatment with IL-15 caused eradication of established tumours in all treated mice. The combined treatment with B78/IL-12 cells and IL-15 activated not only a local response against tumour, but also induced systemic antitumour immunity that led to a delay or inhibition of tumour development at a distant site. In vitro studies demonstrated that when used together, B78/IL-12 cells and IL-15 induced a shift from a type Th2 to a type Th1 response. Activation of the antitumour immune response in double-treated mice resulted, in part, from stimulation of IFN-γ production and was accompanied by the development of cytotoxic effectors in the spleen. As shown in a macrophage tumouricidal assay, macrophages could also play a role in the antitumour effects. The results confirmed that vaccination with IL-12 gene-modified tumour cells is superior to the treatment with unmodified tumour cell vaccine and, additionally, showed that IL-15 is an excellent candidate for adjuvant therapy, inducing synergistically not only a delay of tumour growth but also its complete eradication.
- Subjects
TUMORS; CELLS; CANCER cells; MELANOMA; CANCER; LABORATORY mice; IMMUNIZATION
- Publication
Cancer Immunology, Immunotherapy, 2004, Vol 53, Issue 4, p363
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-003-0449-9