title: Modulation of immune parameters in patients with metastatic renal-cell cancer receiving combination immunotherapy (IL-2, IFN alpha and autologous IL-2-activated lymphocytes).
abstract: We treated 72 patients with metastatic renal-cell cancer according to 2 protocols consisting of two 5-week induction cycles of continuous i.v. high-dose interleukin-2 (IL-2), i.m. interferon-alpha (IFN alpha) and ex vivo IL-2-activated lymphocytes, followed for patients with stable disease (SD), partial response (PR) or complete response (CR) by four 4-week maintenance cycles of IL-2 and IFN alpha. Protocol 2 (55 patients) differed from protocol 1 (17 patients) in (i) the addition of IFN alpha to the first IL-2 infusions in both induction cycles; (ii) the use of Teceleukin IL-2, reconstituted with carrier protein, instead of Proleukin IL-2 without carrier protein. We classified 23 patients with CR and PR as responders (4 in protocol 1 and 19 in protocol 2) and 45 patients with SD and progressive disease as non-responders. Prior to immunotherapy, patients entered into protocol 2 already had higher IFN gamma serum concentrations, higher peripheral blood CD56-,3+ and CD8-,4+ lymphocyte numbers and lower NKK562 activity than those entered into protocol 1. These differences persisted during and after immunotherapy. In line with these observations, ex vivo IL-2-activated lymphocytes had larger proportions of CD56-,3+ and CD8-,4+ lymphocytes and lower NKK562 activity in protocol 2 than in protocol 1. Higher IL-2 serum concentrations were reached during the IL-2 infusion in protocol 2 than in protocol 1. In addition, the immunomodulation in protocol 2 was stronger than in protocol 1 as indicated by higher TNF alpha serum concentrations and a more pronounced eosinophilia. Differences between responders and non-responders treated according to the 2 protocols were not significant, except for the total number of lymphocytes obtained by apheresis, which was higher in responders than in non-responders.
authors.affiliation: Department of Clinical and Tumor Immunology, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: Gratama
authors.forename: P I
authors.initials: PI
authors.lastname: Schmitz
authors.forename: S H
authors.initials: SH
authors.lastname: Goey
authors.forename: C H
authors.initials: CH
authors.lastname: Lamers
authors.forename: G
authors.initials: G
authors.lastname: Stoter
authors.forename: R L
authors.initials: RL
authors.lastname: Bolhuis
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000276:immunology* / Q000628:therapy; D002452:Cell Count; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D016898:Interferon-alpha / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood / Q000276:immunology* / Q000628:therapy; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000637:transplantation; D016131:Lymphocyte Subsets; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis
chemical_list: D016207:Cytokines; D016898:Interferon-alpha; D007376:Interleukin-2