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CTLA-4 blockade enhances antitumor immunity of intratumoral injection of immature dendritic cells into irradiated tumor in a mouse colon cancer model.
- Source :
-
Journal of immunotherapy (Hagerstown, Md. : 1997) [J Immunother] 2014 Jan; Vol. 37 (1), pp. 1-7. - Publication Year :
- 2014
-
Abstract
- Dendritic cells (DCs)-based cancer immunotherapy has been used various strategies to inhibit immune suppressive mechanisms. CD25 antibodies and cyclophosphamide are well-studied immunomodulators through inhibition of regulatory T cells (Treg) and a blockade the immune-checkpoint molecule, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) was recently targeted for immunomodulation. We used anti-CTLA-4 antibody, which is known to induce effective antitumor immunity by facilitating tumor-specific T-cell activation and suppressing Treg cells, as useful immunomodulator to provide a potentiating effect in the intratumoral injection of immature DCs (iDCs) into the irradiated tumor (IR/iDC). Ionizing radiation (IR) was applied at a dose of 10 Gy to the tumor on the right thigh of mice. Then, iDCs were intratumorally injected into the irradiated tumor. Anti-CTLA-4 antibody (100 µg/mouse) was administered intraperitoneally to mice on the same day with every iDCs injection. The growth of distant tumors was inhibited by IR/iDC and this effect was significantly augmented by combination treatment of anti-CTLA-4 antibody. Furthermore, the survival rate of tumor-bearing mice improved more by the combination treatment of anti-CTLA-4 antibody and IR/iDC compared with other groups. It was related to the increased tumor-specific interferon-γ-secreting T cells and CTL activity. Therefore, our results demonstrated that immunomodulator such as anti-CTLA-4 antibody enhances antitumor immunity of intratumoral injection of iDCs into irradiated tumor and suggested a new strategy to get more clinical benefits for cancer treatment.
- Subjects :
- Animals
Antibodies, Monoclonal immunology
CTLA-4 Antigen immunology
Cell Line, Tumor
Colonic Neoplasms mortality
Colonic Neoplasms radiotherapy
Colonic Neoplasms therapy
Disease Models, Animal
Immunotherapy, Adoptive
Interferon-gamma biosynthesis
Lymphocyte Activation drug effects
Lymphocyte Activation immunology
Male
Mice
T-Lymphocytes, Cytotoxic immunology
Th1 Cells drug effects
Th1 Cells immunology
Antibodies, Monoclonal pharmacology
CTLA-4 Antigen antagonists & inhibitors
Colonic Neoplasms immunology
Dendritic Cells immunology
Dendritic Cells transplantation
Subjects
Details
- Language :
- English
- ISSN :
- 1537-4513
- Volume :
- 37
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of immunotherapy (Hagerstown, Md. : 1997)
- Publication Type :
- Academic Journal
- Accession number :
- 24316550
- Full Text :
- https://doi.org/10.1097/CJI.0000000000000007