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/interleukin 3 (GM-CSF/IL-3) genetically engineered hybrid, has shown greater biological activity in stimulating committed myeloid progenitors than either GM-CSF or IL-3 in vitro, in vivo, and in patients treated with high-dose chemotherapy. However, one concern is that PIXY321 may stimulate 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 solid tumors and Hodgkin's or non-Hodgkin's lymphomas. Of the 34 evaluable specimens, including 15 breast cancers, 5 ovarian cancers, 5 lung cancers, and 9 lymphomas, none showed stimulation of tumor growth. Interestingly, a significant inhibition of the tumor proliferation was seen in one breast cancer and in one large cell immunoblastic non-Hodgkin'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 ovary.
Izquierdo
M A
MA
Cancer Therapy and Research Center of South Texas, Institute for Drug Development, San Antonio, Texas 78229, USA.
Degen
D
D
Raymond
E
E
Caron
D
D
Ortiz
V
V
Banks
P
P
Von Hoff
D D
DD
D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology; D008223:Lymphoma / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects*; D010051:Ovarian Neoplasms / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014410:Tumor Stem Cell Assay
D007377:Interleukin-3; C078524:PIXY321 fusion protein, recombinant; D011993:Recombinant Fusion Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor