Modulation of the immunostimulating effect of autologous tumor vaccine by anti-TGF-beta antibody and interferon-alpha on murine MBT-2 bladder cancer.

Unlabelled: 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.

Materials And 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.

Conclusion: 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.