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Modulation of immune parameters in patients with metastatic renal‐cell cancer receiving combination immunotherapy (IL‐2, IFNα and autologous IL‐2‐activated lymphocytes)
Author(s) -
Gratama Jan W.,
Schmitz Paul I. M.,
Goey S. Hoo,
Lamers Cor H. J.,
Stoter Gerrit,
Bolhuis Reinder L. H.
Publication year - 1996
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19960117)65:2<152::aid-ijc5>3.0.co;2-y
Subject(s) - immunotherapy , medicine , cd8 , immune system , immunology , lymphocyte , interleukin 2
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‐α (IFNα) 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 IFNα. Protocol 2 (55 patients) differed from protocol 1 (17 patients) in (i) the addition of IFNα 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 IFNγ serum concentrations, higher peripheral blood CD56 − ,3 + and CD8 − ,4 + lymphocyte numbers and lower NK K562 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 NK K562 activity in protocol 2 than in protocol 1. Higher IL‐2 serum concentrations were reached during the IL‐2 infusions in protocol 2 than in protocol 1. In addition, the immunomodulation in protocol 2 was stronger than in protocol 1 as indicated by higher TNFα 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. © 1996 Wiley‐Liss, Inc.