Formalin-fixed tumor cells effectively induce antitumor immunity both in prophylactic and therapeutic conditions.

Abstract

BACKGROUND:

Autologous whole tumor cell-based vaccinations would seem to be ideal since such vaccinations, in contrast to vaccination with a single defined antigen, have the potential to elicit a broad type of T-cell immune response to tumor-associated antigens.

OBJECTIVE:

We modified formaldehyde (formalin)-fixed mouse melanoma cells and investigated the utility of those cells as sources of tumor antigens for immunotherapy.

METHODS:

C57BL/6 or the proteasome activator PA28alpha-knockout mice were intradermally inoculated with 1% formalin-fixed B16 cells three times at weekly intervals either before or after tumor challenge. Simultaneously, interleukin-12 gene was transferred into the skin around immunization sites using gene gun technology. The effects were evaluated by tumor growth, antigen-specific interferon-gamma production in splenic lymphocytes, and activation of dendritic cells.

RESULTS:

Fixed cells directly induced production of tumor necrosis factor-alpha in dendritic cells more effectively than did frozen and thawed cells. More than 60% of the mice immunized with fixed cells and interleukin-12 rejected the challenged B16 tumor. CD4+ T cells from those mice produced a significant amount of interferon-gamma in response to melanoma cells. Furthermore, this combined treatment showed antitumor immunity initiated by CD8+ and CD4+ T cells in the therapeutic experiments. PA28alpha/beta appeared not to be required for the development of CD8+ T cells, although it is known to be essential for the development of CD8+ T cells specific for tyrosinase-related protein-2, one of melanocyte-lineage differentiated antigens.

CONCLUSION:

These results suggest that formalin-fixed autologous melanoma cells have a potential to function as effective antigen sources for immunotherapy.

• Authors: Chikage Obata, Manxin Zhang, Yoichi Moroi, Hajime Hisaeda, Keiji Tanaka, Shigeo Murata, Masutaka Furue, Kunisuke Himeno
• Journal: Journal of dermatological science (J Dermatol Sci) Vol. 34 Issue 3 Pg. 209-19 (May 2004) ISSN: 0923-1811 [Print] Netherlands
• PMID: 15113591 (Publication Type: Journal Article)
• Copyright: Copyright 2004 Japanese Society for Investigative Dermatology

Chemical References

• Cancer Vaccines
• Fixatives
• Proteins
• Interleukin-12
• Formaldehyde
• Interferon-gamma
• Proteasome Endopeptidase Complex
• Psme1 protein, mouse

Topics

• Animals
• Bone Marrow Cells (cytology, immunology)
• CD4-Positive T-Lymphocytes (immunology, metabolism)
• CD8-Positive T-Lymphocytes (immunology)
• Cancer Vaccines (immunology, pharmacology)
• Cell Death (immunology)
• Female
• Fixatives
• Formaldehyde
• Interferon-gamma (metabolism)
• Interleukin-12 (immunology)
• Melanoma (immunology, prevention & control, therapy)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Proteasome Endopeptidase Complex
• Proteins (genetics)
• Skin Neoplasms (immunology, prevention & control, therapy)
• Spleen (cytology, immunology)
• Tumor Cells, Cultured