Original Articles ADOPTIVE IMMUNOTHERAPY FOR SUPERFICIAL BLADDER CANCER WITH AUTOLOGOUS MACROPHAGE ACTIVATED KILLER CELLS

Purpose: We assessed the efficacy and safety of adoptive immunotherapy administered to 17 patients with TaGIII or recurrent TaGII superficial bladder cancer following transurethral tumor resection. Materials and Methods: Macrophage activated killer (MAK) cells were obtained from autologous mononuclear cells harvested by apheresis, after in vitro culture for 7 days and activation with interferon- on the last day of culture. The patients received 6 weekly intravesical infusions of approximately 2 10 8 cells each. Additionally, 5 patients received 2 or 3 more infusions at 3-month intervals. Each patient was followed for 1 year or until tumor recurrence, whichever came first. Results: A total of 112 intravesical infusions were performed. During the 12-month followup period 8 patients experienced 11 common toxicity criteria grade 1 or grade 2 adverse events considered possibly related to protocol. No clinically relevant grade 1 or 2 laboratory test results were reported while the patients received treatment. In 17 patients 8 tumors recurred compared to 34 recurrences during the year before the first MAK cell infusion. This difference was highly significant (p 0.0005). Conclusions: The promising efficacy and safety results of this study and the fact that the MAK cell treatment regimen proved feasible should encourage initiation of further large scale studies to confirm these data. Activated macrophages are capable of selectively lysing tumor cells, in particular after activation with interferon.1, 2 The antitumoral properties of activated macrophages, or macrophage activated killer (MAK) cells, have been demonstrated in vitro in murine experimental models including nude mice xenografted with human tumors.3, 4 MAK cells can be obtained by in vitro culture of blood monocytes harvested by apheresis. Standardized procedures and quality controlled devices (MAK Cell Processor, IDM, Paris, France) have been developed to make the complete process reproducible and to control the quality of the final cell preparations.5 Clinical trials conducted on a variety of patients with cancer with systemic (intravenous) or local (intraperitoneal or intrapleural) administrations of macrophages have shown that these

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