EFFECTS OF PIXY321, A GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR INTERLEUKIN-3 FUSION PROTEIN, ON HUMAN TUMOR COLONY-FORMING-UNITS TAKEN DIRECTLY FROM PATIENTS

PIXY321, a granulocyte-macrophage colony-stimulating factor/interleuki n 3 (GM-CSF/IL-3) genetically engineered hybrid, has shown greater bio logical activity in stimulating committed myeloid progenitors than eit her GM-CSF or IL-3 in vitro, in vivo, and in patients treated with hig h-dose chemotherapy, However, one concern is that PIXY321 may stimulat e the proliferation of malignant cells which have functional GM-CSF or IL-3 receptors, Therefore, using a human tumor cloning assay, we have tested the effects of several concentrations of PIXY321 ranging from 0.1 to 100 ng/ml on tumor cells taken directly from 98 patients with s olid tumors and Hodgkin's or non-Hodgkin's lymphomas, Of the 34 evalua ble specimens, including 15 breast cancers, 5 ovarian cancers, 5 lung cancers, and 9 lymphomas, none showed stimulation of tumor growth, Int erestingly, a significant inhibition of the tumor proliferation was se en in one breast cancer and in one large cell immunoblastic non-Hodgki n's lymphoma after continuous exposure of PIXY321, In conclusion, the use of PIXY321 to reduce myelosuppression after high-dose chemotherapy appears unlikely to result in stimulation of the growth of malignant cells in patients with lymphoma or cancers of the breast, lung, and ov ary.