Adoptive immunotherapy of experimental tumors using cytotoxic lymphocytes to carry and deliver toxins

Adoptive transfer of specifically sensitized lymphoid cells constitutes a potential tool for specific cancer immunotherapy, however, the requirement of syngeneic or autologous specifically reactive cells has limited its use in the treatment of human cancer. In several mouse tumor models, large amounts of lymphokine activated killer (LAK) cells associated with high doses of interleukin 2 (IL-2) are able to mediate the regression of established pulmonary and hepatic metastases. Since LAK cells are more easily generated than specifically sensitized lymphocytes and show broad tumor specificity, this approach has been applied in humans to treat cancer, but the acute toxicity associated with the high doses of IL-2 administered represents an important drawback to its clinical use. The observation that lymphocytes can internalize ricin, a toxic plant protein, and then release it in an active form, capable of destroying other cells, led us to investigate the possibility of using antigen-specific cytotoxic T lymphocytes (CTL) or LAK cells as carriers of toxic substances to the tumor site. In our experimental models we observed that tumor-specific CTL or LAK cells can be used to deliver ricin into the tumor mass and cause temporary tumor growth inhibition.