TY - JOUR
T1 - Formalin-fixed tumor cells effectively induce antitumor immunity both in prophylactic and therapeutic conditions
AU - Obata, Chikage
AU - Zhang, Manxin
AU - Moroi, Yoichi
AU - Hisaeda, Hajime
AU - Tanaka, Keiji
AU - Murata, Shigeo
AU - Furue, Masutaka
AU - Himeno, Kunisuke
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2004/5
Y1 - 2004/5
N2 - 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 PA28α-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-γ production in splenic lymphocytes, and activation of dendritic cells. Results: Fixed cells directly induced production of tumor necrosis factor-α 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-γ in response to melanoma cells. Furthermore, this combined treatment showed antitumor immunity initiated by CD8+ and CD4 + T cells in the therapeutic experiments. PA28α/β 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.
AB - 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 PA28α-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-γ production in splenic lymphocytes, and activation of dendritic cells. Results: Fixed cells directly induced production of tumor necrosis factor-α 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-γ in response to melanoma cells. Furthermore, this combined treatment showed antitumor immunity initiated by CD8+ and CD4 + T cells in the therapeutic experiments. PA28α/β 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.
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U2 - 10.1016/j.jdermsci.2004.02.003
DO - 10.1016/j.jdermsci.2004.02.003
M3 - Article
C2 - 15113591
AN - SCOPUS:2142764370
VL - 34
SP - 209
EP - 219
JO - Journal of Dermatological Science
JF - Journal of Dermatological Science
SN - 0923-1811
IS - 3
ER -