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 irradiate d or nonirradiated, express TGF-beta 1 mRNA and secrete TGF-beta 1 pro tein, and b) to investigate whether the adverse effects from IRMBT-2-s ecreting TGF-beta 1 in the tumor vaccine can be abrogated by exogenous addition of monoclonal anti-TGF-beta 1 antibody and/or IFN-alpha. Mat erials 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 ant i-TGF-beta and/or IFN-alpha were studied by an in vitro splenocyte pro liferation assay and in vivo tumor rechallenge study on day 17-TBM. Re sults: 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 si multaneous 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 ob tained in groups of mice treated with postoperative vaccination with a nti-TGF-beta modified tumor vaccine with or without an additional admi nistration 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.