ADOPTIVE IMMUNOTHERAPY WITH TUMOR-CYTOTOXIC MACROPHAGES DERIVED FROM RECOMBINANT HUMAN GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR (RHUGM-CSF) MOBILIZED PERIPHERAL-BLOOD MONOCYTES

We examined the mobilization of blood monocytes (MO) with recombinant human granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) wit h regard to the in vitro generation of MO-derived tumor-cytotoxic macr ophages (MAC) for use in adoptive immunotherapy of cancer patients. El even patients with progressing metastatic cancer received interferon ( IFN)-gamma activated tumor-cytotoxic MAC generated in vitro from autol ogous MO with and without pretreatment with rhuGM-CSF. RhuGM-CSF was a dministered subcutaneously at 10 mu g/kg for 7 days. RhuGM-CSF treatme nt and adoptive cell transfer were well tolerated, and no toxicity gre ater than WHO IIO occurred. Fever was the most common side effect and was seen in all patients during rhuGM-CSF treatment and during 9 of 22 MAC therapies, Bone pain was noted in 5 of 11 patients during rhuGM-C SF therapy. RhuGM-CSF treatment led to a continuous increase in the wh ite blood cell counts and the number of MO within the leukapheresis pr oducts. The mean number of transfused MAC was 0.9 x 10(9) without rhuG M-CSF pretreatment and 1.9 x 10(9) after rhuGM-CSF administration. The maximum number of MAC that could be generated was 7.3 x 10(9), but af ter a dose escalation protocol only up to 2.7 x 10(9) MAC were transfu sed. Cytotoxicity against U937 cells increased during MO to MAC differ entiation, but was decreased in both MO and MAC on treatment with rhuG M-CSF. This study proves the feasibility of reinfusing MAC generated i n vitro from rhuGM-CSF mobilized MO.