Biological response modifiers: regulators of the cellular immune system and adjuvants in antitumor therapy.
Pharmacokinetic studies of five biological response modifiers (BRMs) show diverse regulator functions on effector cell responses and a capacity to cause the secretion of specific soluble factors. Of the five BRMs tested, MVE-2, Poly ICLC, OK-432, and alpha beta IFN were capable of stimulating both natural killer (NK) cell and macrophage (M phi) tumoricidal activity, whereas BM 41-332 augmented only NK cells. Following one treatment with the aforementioned BRMs, M phi activity remained elevated for a longer period (10-14 days) than did NK cell activity (6-9 days). Of particular interest, multiple treatment with BRMs led to a downregulation of NK cell activity (hyporesponsiveness). Three soluble secretory products were induced by these BRMs (colony stimulating factor, CSF; prostaglandin E, PGE; and interferon, IFN). Treatment with MVE-2 and Poly ICLC led to a significant increase in bone marrow cellularity and GM-CFV-C. Results of studies with the cyclo-oxygense-inhibited indomethacin indicate that CSF and PGE are produced and/or secreted by different cellular mechanisms. The depression of effector cells (NK, bone marrow, and GM-CFU-C), as the result of cyto-reductive treatment with cyclophosphamide, could be reversed by treatment with MVE-2. A significantly earlier time to recovery of these effector cells was achieved following MVE-treatment. When MVE-2 was used as an adjuvant to initial tumor cyto-reductive chemotherapy, more successful antitumor response was achieved, indicating that MVE-2 functioned to elevate a substantial effector cell response as well as reconstituting bone marrow cellularity.
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D007111:Immunity, Cellular / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D003115:Colony-Stimulating Factors; D007213:Indomethacin