Clinical Cancer Research, Vol 2, Issue 10 1713-1716, Copyright © 1996 by American Association for Cancer Research

ARTICLES

Effects of PIXY321, a granulocyte-macrophage colony-stimulating factor/interleukin 3 fusion protein, on human tumor colony-forming units taken directly from patients

MA Izquierdo, D Degen, E Raymond, D Caron, V Ortiz, P Banks and DD Von Hoff
Cancer Therapy and Research Center of South Texas, Institute for Drug Development, San Antonio, Texas 78229, USA.

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.