Modulation of the immunostimulating effect of autologous tumor vaccine by anti-TGF-beta antibody and interferon-alpha on murine MBT-2 bladder cancer.
Our aims were to: a) elucidate whether MBT-2 cells, lethally irradiated or nonirradiated, express TGF-beta 1 mRNA and secrete TGF-beta 1 protein, and b) to investigate whether the adverse effects from IRMBT-2-secreting TGF-beta 1 in the tumor vaccine can be abrogated by exogenous addition of monoclonal anti-TGF-beta 1 antibody and/or IFN-alpha.


METHODS
using the Northern hybridization analysis and the two-antibody sandwich ELISA, we demonstrate that both irradiated IRMBT-2 and nonirradiated MBT-2 cells secrete TGF-beta 1. The effect of anti-TGF-beta and/or IFN-alpha were studied by an in vitro splenocyte proliferation assay and in vivo tumor rechallenge study on day 17-TBM.


RESULTS
Both IRMBT-2 and splenocytes from day 17-TBM secrete TGF-beta 1 which can express suppression of the proliferation of the splenocytes from day 17-TBM. This suppression can be partially reversed by the simultaneous addition of both anti-TGF-beta and IFN-alpha, either alone being insufficient. The result of the in vivo tumor rechallenge study on day 17-TBM reveals that a lower tumor outgrowth incidence can be obtained in groups of mice treated with postoperative vaccination with anti-TGF-beta modified tumor vaccine with or without an additional administration of IFN-alpha.


CONCLUSIONS
Apart from TGF-beta, MBT-2 cells, both irradiated and nonirradiated, may also secrete other suppressive factors that adversely downregulate the immune response of TBM which can not then be adequately reversed by IFN-alpha.
Tzai
T S
TS
Department of Urology, Medical College, National Cheng Kung University, Tainan, Taiwan, Republic of China.
Shiau
A L
AL
Lin
C S
CS
Wu
C L
CL
Lin
J S
JS
D000818:Animals; D015152:Blotting, Northern; D019496:Cancer Vaccines / Q000276:immunology*; D005260:Female; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D001749:Urinary Bladder Neoplasms / Q000276:immunology* / Q000378:metabolism
D019496:Cancer Vaccines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta