Antineoplastic treatment regimens consisting of chemotherapy often result in a dysfunction of hematopoietic precursor cells of the granulocyte-macrophage (CM-CFU-C) lineage. We were, therefore, interested in testing the ability of selected biological response modifiers (BRMs) to modulate growth and differentiation of BM-CFU-C and nucleated bone marrow cells (BMC) in normal and cyclophosphamide (CY)-pretreated mice. In vivo treatment of normal mice with either MVE-2 or poly ICLC induced an increase in secretion of colony stimulating factor (CSF) by BMC and marcophages, which was followed by an increased proliferation rate of BM-CFU-C and BMC. Both BRMs were also able to ameliorate the bone marrow depressing effects of CY pretreatment and to induce significantly enhanced MPhi activities when given about 3 days after CY. Second, it has been established that MVE-2 can CSF-mediated anti-tumor on certain leukemic tumor cells. In vivo experiments showed that treatment of mice bearing the Wehi-3 differentiation positive myelomonocytic tumor first with CY and then 3 days later with the potent CSF-inducer MVE-2 incrased survival time significantly, rendered 20-50 % of the tumor-bearing mice disease-free. No effects were seen with the differentiation negative tumors. The present results support the concept that selected BRMs might be of value in reconstituting granulocyte and macrophage functions, and may further prevent leukeogensis by induction of terminal differentiation. Attempts have also been made to identify whether immortalized human T cells secrete growth factors are essential for long-term growth of human pluripotent hematapoietic stem cells in vitro. Identification of such factors (e.g. multi CSF) provide a model for studying physiologic regulation of marrow cell growth and differentiation and could also allow sustain proliferating stem cells in vitro as a source of BMC after treatment with chemotherapy. Preliminary evidence suggest that an autocrine regulation of tumor growth exists. Two murine tumors (a Moloney virus-transformed T lymphoma and a spontaneous lung carcinoma) secrete factors that stimulate their own growth in a clonogenic assay and in suspension culture. These findings could provide the basis for trying to interfere with the respective tumor growth, e.g. by inhibiting the factor(s) or their production.
