Back to Search
Start Over
Combination of two fiber-mutant adenovirus vectors, one encoding the chemokine FKN and another encoding cytokine interleukin 12, elicits notably enhanced anti-tumor responses.
- Source :
-
Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2008 Nov; Vol. 57 (11), pp. 1657-64. Date of Electronic Publication: 2008 Mar 08. - Publication Year :
- 2008
-
Abstract
- For achieving optimal cancer immunotherapy, it is anticipated that both the activation and infiltration of immune cells into tumor are indispensable. In the present study, fiber-mutant adenovirus vectors (Ad) encoding chemokine FKN, (AdRGD-FKN), and cytokine interleukin 12, (AdRGD-IL-12), were constructed. The in vivo gene expression of AdRGD was confirmed and the combination of both FKN and IL-12 encoding Ad elicited synergistic anti-tumor activity in ovarian carcinoma, which induced tumor regression in all tumor-bearing mice, while using FKN alone did not show notable tumor-suppressive effect. The treatment with both IL-12 and FKN induced long-term specific immunity against OV-HM tumors in tumor-rejected mice. The results of immunohistochemical staining for CD3+ and perforin-positive cells suggested that the failure of using FKN alone was because of the inactivation of infiltrated immune cells. In contrast, cotransduction with IL-12 and FKN could induce more activated tumor-infiltrating immune cells than that transducted with FKN or IL-12 alone. The results indicated that using both chemokine and cytokine might be a powerful tool and a promising way for effective cancer immunotherapy.
- Subjects :
- Animals
Antineoplastic Agents therapeutic use
Drug Therapy, Combination
Female
Green Fluorescent Proteins genetics
Interferon-gamma metabolism
Interleukin-11 Receptor alpha Subunit immunology
Interleukin-12 immunology
Lymphocytes, Tumor-Infiltrating immunology
Lymphocytes, Tumor-Infiltrating metabolism
Lymphocytes, Tumor-Infiltrating pathology
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Oligopeptides genetics
Ovarian Neoplasms immunology
Adenoviridae genetics
Genetic Therapy
Genetic Vectors therapeutic use
Interleukin-11 Receptor alpha Subunit genetics
Interleukin-12 genetics
Ovarian Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 0340-7004
- Volume :
- 57
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Cancer immunology, immunotherapy : CII
- Publication Type :
- Academic Journal
- Accession number :
- 18327579
- Full Text :
- https://doi.org/10.1007/s00262-008-0499-0