Phase I evaluation of a combination of monoclonal antibody R24 and interleukin 2 in patients with metastatic melanoma.
A combination of recombinant human interleukin 2 (rhIL-2) and mouse monoclonal antibody R24 (recognizing the ganglioside GD3) was evaluated in patients with metastatic melanoma in a phase I trial. rhIL-2 was given at a constant daily dose of 1 x 10(6) units/m2 i.v. over 6 h on days 1-5 and 8-12. R24 was given on days 8-12 at four dose levels (1, 3, 8, and 12 mg/m2 daily). Twenty patients were evaluable for toxicity and response, five at each dose level. The toxicity of the combination was not overlapping and generally mild. There was a rebound peripheral blood T-lymphocytosis at the end of treatment increasing with the dose of R24. The median lymphocyte count on day 12 of treatment was 3108 +/- 554/ml in patients treated at R24 doses of 8 and 12 mg/m2 versus 2239 +/- 672/ml at doses of 1 and 3 mg/m2. This evidence and other data suggested that R24 enhanced IL-2-mediated T-cell activation in vivo. Two patients demonstrated increases in R24-mediated antibody-dependent cellular cytotoxicity for GD3-expressing cells during treatment. rhIL-2 appeared to accelerate the development of human anti-mouse antibody; three patients developed human anti-mouse antibody by the fifth day of R24 treatment, earlier than observed in prior studies using R24 alone and one patient during the first week of rhIL-2 alone, prior to R24 treatment. One patient had a partial response in soft tissue sites lasting 6 months and two patients had minor responses. This clinical trial extends the previous observation that R24 enhances lymphocyte proliferation in vitro.
Bajorin
D F
DF
Clinical Immunology Service, Memorial Sloan-Kettering Cancer Center, New York, New York.
Chapman
P B
PB
Wong
G
G
Coit
D G
DG
Kunicka
J
J
Dimaggio
J
J
Cordon-Cardo
C
C
Urmacher
C
C
Dantes
L
L
Templeton
M A
MA
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000276:immunology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D011994:Recombinant Proteins
D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D011994:Recombinant Proteins