Article révisé par les pairs
Résumé : Intravcsical BCG is an effective treatment for superficial bladder cancer. However its mechanism of action is still partially unknown. Live but not killed BCG has been demonstrated to induce killer cells against bladder tumour cells. We studied whether culture filtrate from BCG culture (CF) could enhance lymphocyte-mediated bladder tumour cell killing in an MHC-unrestricted manner in man and in mice. Human peripheral blood mononuclear cells (PBMC) and splenocytes from C3H mice (H-2k) were incubated with or without BCG, CF or Interleukin-2 (15U/ml) for 7 days. A neutral red dye uptake or a Chromium 51 release assay were used to assess cytotoxicity of these amplified effector cells against T24 bladder tumour cells in man and against MBT2 cells (murine C3H bladder tumour). All measurements and experiments were done in triplicate. In man, cytotoxicity against T24 cells induced by PBMC incubated with BCG. CF, IL-2 and culture medium (controls) was on average 82.6%, 83.3%, 88.5% and 38.3% respectively. These effects were inhibited by depletion of CD56 cells. In mice, against MBT2 cells, cytotoxicity induced by splenocytes incubated with BCG, CF, 11-2 and culture medium was 97.6%, 97.2%, 85.4% and 32.9% respectively. Supcrnatants from BCG, CF, IL-2 activated PBMC or mouse splenocytes induced less than 10 % and less than 20% of the cytotoxic activity respectively. In vitro, BCG culture filtrate is as effective as live BCG to enhance lymphocyte mediated cytotoxicity against bladder tumour cells both in man and in mice. The lack of effectiveness of dead BCG could be related to the absence of secretion by the bacteria of immunologically active components. In vivo use of culture filtrate from BCG is currently under study in mice carrying MBT2 tumours. Our data suggest that live BCG intravesical therapy could be replaced in the future by purified BCG components.