title: Expansion of peripheral blood natural killer cells correlates with clinical outcome in cancer patients receiving recombinant subcutaneous interleukin-2 and interferon-alpha-2.
abstract: Natural killer (NK) cells are believed to contribute to the clinical efficacy of cancer immunotherapy using recombinant interleukin-2 (rIL-2) in humans. In previous trials of high-dose i.v. rIL-2, however, no correlation has been established between circulating NK cells and treatment response. Between January 1989 and October 1990, we treated a total of 47 outpatients with advanced tumors using low-dose s.c. rIL-2 and interferon-alpha-2 (rIFN-alpha). Therapy consisted of a 2-day rIL-2 pulse at 18 million IU/m2/day, followed by 6 weeks of rIL-2 (3.6 x 10(6)-4.8 x 10(6) IU/m2/day x 5 days/week) and rIFN-alpha (5 x 10(6)-6 x 10(6) U/m2 x 3/week). Before and after therapy, we phenotypically evaluated circulating lymphocytes and correlated them with clinical response. During 6-week therapy, peripheral blood lymphocytes bearing the CD56 (NK-cell-associated) surface antigen were increased significantly (p < or = 0.005) in treatment responders [complete response (CR) and partial response (PR), n = 10; 3.8-fold] and stable disease (SD) patients (n = 20; 2.1-fold), while patients with progressive disease (PD, n = 17) exhibited no significant expansion of circulating NK cells (p > 0.1). After one 6-week treatment cycle, CR/PR patients had significantly more peripheral NK cells, when compared with patients in SD (1.6-fold) and PD (1.9-fold) (p < 0.04). The overall number of circulating lymphocytes was also increased upon therapy (1.6-fold; p < or = 0.001), but remained independent of response (p > 0.4). These data demonstrate that s.c. rIL-2 and s.c. rIFN-alpha produce a significant increase in peripheral blood NK cells; this expansion correlates significantly with treatment response in advanced tumor patients receiving long-term combination immunotherapy at outpatient doses.
authors.affiliation: Department of Hematology and Oncology, MHH University Medical Center, Hannover, FRG.
authors.forename: J
authors.initials: J
authors.lastname: Atzpodien
authors.forename: H
authors.initials: H
authors.lastname: Kirchner
authors.forename: A
authors.initials: A
authors.lastname: Körfer
authors.forename: M
authors.initials: M
authors.lastname: Hadam
authors.forename: A
authors.initials: A
authors.lastname: Schomburg
authors.forename: T
authors.initials: T
authors.lastname: Menzel
authors.forename: M
authors.initials: M
authors.lastname: Deckert
authors.forename: A
authors.initials: A
authors.lastname: Franzke
authors.forename: M
authors.initials: M
authors.lastname: Volkenandt
authors.forename: I
authors.initials: I
authors.lastname: Dallmann
mesh_terms: D015703:Antigens, CD / Q000097:blood; D002292:Carcinoma, Renal Cell / Q000628:therapy; D015179:Colorectal Neoplasms / Q000628:therapy; D004334:Drug Administration Schedule; D006689:Hodgkin Disease / Q000628:therapy; D006801:Humans; D016130:Immunophenotyping; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000628:therapy; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D016393:Lymphoma, B-Cell / Q000628:therapy; D008545:Melanoma / Q000628:therapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D016176:T-Lymphocyte Subsets / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D015703:Antigens, CD; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins