title: Effect of ASTA-Z 7575 (INN Maphosphamide) on human lymphokine-activated killer cell induction.
abstract: Recent studies combining chemotherapeutic agents with various biological response modifiers for the treatment of cancer have shown promising results. Cyclophosphamide (Cy) is the most widely used alkylating agent and a major constituent of combination chemotherapy regimens for many neoplastic diseases. It has been reported that Cy is a cytotoxic drug, which becomes immunosuppressive at higher doses. A synthetic metabolite of Cy, ASTA-Z, has recently been produced. ASTA-Z is more active and stable by itself and does not need to be metabolically converted to an active compound. The combined effect of Cy and interleukin-2 (IL-2) on the induction of lymphokine-activated killer (LAK) cells is not known. Therefore, we decided to investigate the effect of ASTA-Z on the induction and function of LAK. The coculture of peripheral blood mononuclear cells (PBMC) with various concentrations of ASTA-Z (0, 10(-6), 10(-5), 10(-4), and 10(-3) dilution) and IL-2 (50 U/ml) for 4 days produced significant suppression of cytotoxicity and lytic ability of the LAK cells against NK-sensitive (K562) and NK-resistant (M14) tumor cell lines. The lower doses of ASTA-Z did not affect the generation of LAK cells, its cytotoxicity and lytic ability of ASTA-Z against both NK-sensitive and NK-resistant tumor cell lines. Furthermore, the ASTA-Z produced dose-dependent suppression of the proliferative response of LAK cells. The significant therapeutic benefit in the cancer patient may be achieved by the low dose regimen of Cy and IL-2 because it has no deleterious effect on the induction and function of LAK cells.
authors.affiliation: Preventive Toxicology Division, Industrial Toxicology Research Centre, Lucknow, India.
authors.forename: K P
authors.initials: KP
authors.lastname: Singh
authors.forename: R K
authors.initials: RK
authors.lastname: Gupta
authors.forename: H
authors.initials: H
authors.lastname: Shau
authors.forename: P K
authors.initials: PK
authors.lastname: Ray
mesh_terms: D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000276:immunology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; D007376:Interleukin-2; C048341:mafosfamide; D003520:Cyclophosphamide