Intrahepatic adoptive immunotherapy with autologous tumorcytotoxic macrophages in patients with cancer.

Abstract

Adoptive transfer of cytotoxic macrophages (MAC) may be able to correct for a defective generation of competent effector cells in patients with cancer. Here we report on a Phase I trial of adoptive transfer of autologous MAC by hepatic artery infusion in seven patients with metastatic liver disease. Clinical side effects were mild and consisted of fever and flu-like symptoms. Serum levels of C-reactive protein (CRP) increased within hours after MAC transfer and rose further in the course of repeated therapies. An increase of thrombin-anti-thrombin III complexes occurred in 31% of therapies. Serum neopterin, interleukin (IL)-6, and IL-8 did not change during therapy. In vivo tracing of 111 indium-labeled MAC revealed that on average, 43% of whole-body activity remained in the liver for 7 days. Evidence for tumor response could not be demonstrated. In conclusion, isolated liver perfusion with autologous MAC is well tolerated and induces a profound biological response in the recipient. Regional adoptive immunotherapy might be able to built up, in proximity to metastatic lesions, a potent cytotoxic cell infiltrate that could then be triggered within the patient using exogenous stimuli like endotoxin, cytokines, or other MAC activators.