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Local administration of IL-12-transfected dendritic cells induces antitumor immune responses to colon adenocarcinoma in the liver in mice.
- Source :
-
Journal of experimental therapeutics & oncology [J Exp Ther Oncol] 2002 Nov-Dec; Vol. 2 (6), pp. 337-49. - Publication Year :
- 2002
-
Abstract
- Colorectal cancer is one of the most common fatal malignancies in the United States, with an incidence second only to lung cancer. The liver is the most common site of colorectal metastases and frequently the only affected organ once the primary tumor has been surgically removed. The only potentially curative treatment for metastatic colorectal cancer in the liver is surgery, although most patients are not eligible for resection. We have therefore, evaluated the therapeutic efficacy of dendritic cells (DCs) engineered to express IL-12 in a liver metastasis model. Direct administration of DCs into the portal vein significantly inhibited the growth of established MC38 colon carcinoma in the liver in C57BL/6 mice. This effect was accompanied by an intratumoral accumulation of CD4+, CD8+, and NLDC-145+ immune effector cells, and also resulted in a systemic immune response as determined by enhanced production of IFN-gamma by T lymphocytes isolated from both spleen and draining lymph nodes. Evaluation of homing of Cy3-labeled DCs following the portal vein injection confirmed their distribution in the liver and lymphoid tissue. Thus, a local delivery of DCs transduced with the IL-12 gene can not only inhibit colorectal tumor growth in vivo but also mount systemic antitumor immune responses. This approach is likely to improve the outcome of immunotherapy for metastatic colorectal cancer since high numbers of tumor-associated DCs positively correlate with a more favorable prognosis. Simultaneous local gene therapy with IL-12 will further improve clinical efficacy without placing the patient at risk for systemic toxicity.
- Subjects :
- Adenocarcinoma immunology
Adenocarcinoma secondary
Adenoviridae genetics
Animals
Antigens, CD immunology
Antigens, CD metabolism
CD4-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes immunology
Cell Division physiology
Colonic Neoplasms immunology
Colonic Neoplasms pathology
Colonic Neoplasms therapy
Dendritic Cells transplantation
Humans
Immunity, Cellular
Interleukin-12 metabolism
Liver Neoplasms, Experimental immunology
Liver Neoplasms, Experimental secondary
Liver Neoplasms, Experimental therapy
Lymph Nodes immunology
Lymph Nodes metabolism
Lymphocyte Activation immunology
Lymphocytes, Tumor-Infiltrating immunology
Male
Mice
Mice, Inbred C57BL
Spleen cytology
Spleen immunology
T-Lymphocytes, Cytotoxic immunology
Transduction, Genetic
Tumor Cells, Cultured immunology
Tumor Cells, Cultured metabolism
Tumor Cells, Cultured transplantation
Adenocarcinoma therapy
Dendritic Cells immunology
Immunotherapy, Adoptive
Interleukin-12 genetics
Transfection
Subjects
Details
- Language :
- English
- ISSN :
- 1359-4117
- Volume :
- 2
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of experimental therapeutics & oncology
- Publication Type :
- Academic Journal
- Accession number :
- 12440225
- Full Text :
- https://doi.org/10.1046/j.1359-4117.2002.01050.x