Exosomes from CIITA-transfected CT26 cells enhance anti- tumor effects.

Abstract

AIM:

To study anti-tumor effects of exosomes from class II transactivator (CIITA) gene transfected CT26 cells.

METHODS:

In this study, we established an MHC class II molecule-expressing murine colon cancer cell line (CT26-CIITA) by transduction of the CIITA gene. Immune effects in vitro and tumor protective results in vivo were tested and monitored.

RESULTS:

Exosomes from CT26-CIITA cells were found to contain a high level of MHC class II protein. When loaded on dendritic cells (DCs), exosomes from CT26-CIITA cells significantly increased expression of MHC class II molecules, CD86 and CD80, as compared to exosomes from CT26 cells. In vitro assays using co-culture of immunized splenocytes and exosome-loaded DCs demonstrated that CIITA- Exo enhanced splenocyte proliferation and IFN-γ production of CD4+T cells, while inhibiting IL-10 secretion. In addition, compared to exosomes from CT26 cells, CT26-CIITA-derived exosomes induced higher TNF-α and IL-12 mRNA levels. A mouse tumour preventive model showed that CT26-CIITA derived exosomes significantly inhibited tumour growth in a dose-dependent manner and significantly prolonged the survival time of tumour- bearing mice.

CONCLUSION:

Our findings indicate that CT26-CIITA-released exosomes are more efficient to induce anti-tumour immune responses, suggesting a potential role of MHC class II-containing tumour exosomes as cancer vaccine candidates.

• Authors: Wen Fan, Xing-De Tian, E Huang, Jia-Jun Zhang
• Journal: Asian Pacific journal of cancer prevention : APJCP (Asian Pac J Cancer Prev) Vol. 14 Issue 2 Pg. 987-91 ( 2013) ISSN: 2476-762X [Electronic] Thailand
• PMID: 23621273 (Publication Type: Journal Article)

Chemical References

• B7-1 Antigen
• B7-2 Antigen
• Cancer Vaccines
• IL10 protein, mouse
• MHC class II transactivator protein
• Nuclear Proteins
• RNA, Messenger
• Trans-Activators
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Interleukin-12
• Interferon-gamma

Topics

• Animals
• B7-1 Antigen (metabolism)
• B7-2 Antigen (metabolism)
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• CD8-Positive T-Lymphocytes (immunology, metabolism)
• Cancer Vaccines
• Cell Line, Tumor
• Cell Proliferation
• Colonic Neoplasms (immunology, metabolism)
• Dendritic Cells (metabolism)
• Disease Models, Animal
• Exosomes (immunology, metabolism)
• Interferon-gamma (blood, metabolism)
• Interleukin-10 (blood, metabolism)
• Interleukin-12 (blood, genetics)
• Mice
• Mice, Inbred BALB C
• Nuclear Proteins (genetics)
• RNA, Messenger (biosynthesis)
• Spleen (cytology, metabolism)
• Trans-Activators (genetics)
• Transfection
• Tumor Necrosis Factor-alpha (blood, genetics)