Ex vivo activation of killer monocytes (AKM) and their application to the treatment of human cancer

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Abstract
Human blood monocytes activated by gamma interferon have been shown to be highly tumoricidal against colon cancer cells in vitro. Monocytes from patients with peritoneal colorectal carcinomatosis (PCC) were purified by a combination of cytapheresis and elutriation procedures, followed by in vitro incubation with gamma interferon for 18 hours. After debulking surgery, activated killer monocytes (AKM) were reinfused into patients' peritoneal cavities weekly for 16 weeks. To date, six patients have completed the entire protocol and three have completed maintenance therapy. All have tolerated the therapy well with acceptable toxicity. Midway through the protocol, we analyzed the trafficking pattern of the AKM by prelabeling them with 111in. Distribution was relatively homogeneous throughout the peritoneum; at the second staging celiotomy, three of the seven PCC patients were found to have very small amounts of recurrent disease in places to which the AKM were felt to have had limited access (other areas remained disease‐free); these areas of recurrent disease were surgically resectable. AKM have also been infused systemically into five cancer patients. First, the patients were infused with unactivated 111in‐labeled monocytes; 1 month later each patient received 111In‐labeled gamma interferon‐activated AKM. Trafficking studies indicated that both forms of monocytes migrated to sites in the reticuloendothelial system. We have seen virtually no complications from intravenous infusions of either unactivated or gamma interferon‐activated AKM. These studies indicate that the adoptive immunotherapy of cancer patients with AKM is a feasible and safe procedure.