Modulation of immune parameters in patients with metastatic renal-cell cancer receiving combination immunotherapy (IL-2, IFN alpha and autologous IL-2-activated lymphocytes)

Int J Cancer. 1996 Jan 17;65(2):152-60. doi: 10.1002/(SICI)1097-0215(19960117)65:2<152::AID-IJC5>3.0.CO;2-Y.


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.

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Renal Cell / blood
  • Carcinoma, Renal Cell / immunology*
  • Carcinoma, Renal Cell / therapy
  • Cell Count
  • Cytokines / blood
  • Female
  • Humans
  • Immunophenotyping
  • Immunotherapy, Adoptive*
  • Interferon-alpha / therapeutic use*
  • Interleukin-2 / therapeutic use*
  • Kidney Neoplasms / blood
  • Kidney Neoplasms / immunology*
  • Kidney Neoplasms / therapy
  • Leukocytes, Mononuclear / immunology*
  • Leukocytes, Mononuclear / transplantation
  • Lymphocyte Subsets
  • Male
  • Middle Aged
  • Neoplasm Metastasis


  • Cytokines
  • Interferon-alpha
  • Interleukin-2