In vivo activation of lymphocytes in melanoma patients receiving escalating doses of recombinant interleukin 2.
A phase-I study of the recombinant, non-mutagenized interleukin 2 (rIL2, BioleukinTM) was performed in 12 melanoma patients (Pts). From 100 to 800 micrograms/m2 of rIL2 were administered by i.v. bolus injection, TID for 4-8 days. Side-effects included fever, malaise, low serum K+ and Ca++ values, electrocardiographic abnormalities, leukopenia and thrombocytopenia. No major organ toxicity and no significant fluid retention were observed at the administered doses. Treatment induced a rapid depletion of peripheral blood lymphocytes (PBL) with a rebound (2-6 times the pre-treatment values), 24-48 hr after rIL2 discontinuation. PBL obtained between the 5th treatment day and the 2nd post-treatment day showed: (a) enhanced proliferation (II/12 Pts) with stimulation indexes of 6-52; (b) increased cytotoxicity against autologous tumor cells (2/2 Pts), allogeneic melanomas (5/7 Pts), the Daudi (5/6 Pts) and K562 cell lines (7/12 Pts); and (c) increased expression of IL2 receptors (8/12 Pts) and of DR antigens (6/12 Pts). Lymphocytes collected 1-2 days after treatment and activated in vitro with rIL2 showed a more rapid development of tumor cytotoxicity, with an earlier loss of activity. Spontaneous proliferation, autologous or allogeneic tumor cytotoxicity and expression of IL2 receptors obtained after in vivo treatment with rIL2 were significantly weaker than those induced during in vitro stimulation. No major objective responses were detected in these patients.
Gambacorti-Passerini
C
C
Division of Experimental Oncology D, Istituto Nazionale Tumori, Milan, Italy.
Radrizzani
M
M
Marolda
R
R
Belli
F
F
Sciorelli
G
G
Galazka
A R
AR
Schindler
J D
JD
Cascinelli
N
N
Parmiani
G
G
D000954:Antigens, Surface / Q000032:analysis; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D004804:Eosinophils / Q000473:pathology; D006801:Humans; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D007700:Kinetics; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D011994:Recombinant Proteins
D000954:Antigens, Surface; D007376:Interleukin-2; D011994:Recombinant Proteins