Abstract
In the interest of developing more effective adoptive immunotherapy, we investigated the effect of cyclophosphamide (Cy) on the induction of tumor-specific cytotoxic T lymphocytes (CTL). When co-cultured with autologous tumor cells, patient peripheral blood mononuclear cells (PBMC) developed the ability to kill either autologous or HLA class I-matched allogeneic tumor cells. This killer activity was completely blocked by pretreatment with an anti-CD3 monoclonal antibody (MAb) plus complement. The CTL activity of PBMC from Cy-treated patients was compared with the activity of cells obtained from the same patients before Cy treatment. It was found that Cy treatment greatly enhanced patient' CTL activity (from 15.9±1.1 to 26.5±1.1% in patient 1 and from 7.6±2.3 to 28.7±2.3% in patient 2: both P<0.001).
We also found the same phenomenon in vitro, since addition of Cy at the initiation of stimulator and effector cultures resulted in enhanced CTL activity. However, addition of Cy after the generation of CTL did not increase CTL activity, suggesting that Cy acts on the induction phase, but not the effector phase of CTL. Thus, our results indicate that Cy can enhance CTL activity and suggest that administration of Cy together with CTL injection may be helpful in developing new forms of adoptive immunotherapy.
