Lack of correlation between peripheral blood lymphokine-activated killer (LAK) cell function and clinical response in patients with advanced malignant melanoma receiving recombinant interleukin 2.
A phase-I/II study of recombinant interleukin 2 (rIL-2) was performed in 31 melanoma patients. The first dose of rIL-2 was given intrasplenically followed 4 hr later by an i.v. dose and 3 further i.v. doses on alternate days. Three courses of treatment were planned at 3-week intervals. The maximum tolerated single dose was 11 x 10(6) Cetus U/m2. Haematological and immunological data were available on 20 patients. Post-treatment response to rIL-2 therapy was evident from (i) a rapid depletion of peripheral blood lymphocytes (PBL) with a rebound at 4-7 days (2 times pre-treatment values); (ii) an increase in the number of IL-2 receptor-positive lymphocytes (4-15 times pre-treatment values); (iii) an increase in the number of "positive" patients with cytotoxic (anti-K562) peripheral blood mononuclear cells (PBMC) from 30% to 80%; (iv) amplified killing of K562 by positive patients in relation to pre-treatment values; and (v) the induction of PBMC cytotoxicity (in 45% of patients) against the NK-resistant, LAK-sensitive target, Mel I. Partial clinical responses to rIL-2 treatment were observed in 4 patients, but these were not reflected in the PBMC LAK activity or the other parameters examined.
Ghosh
A K
AK
Cancer Research Campaign, Paterson Institute for Cancer Research, Christie Hospital, Manchester, UK.
Dazzi
H
H
Thatcher
N
N
Moore
M
M
D003602:Cytotoxicity, Immunologic; D004341:Drug Evaluation; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology*; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008214:Lymphocytes; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D010641:Phenotype; D015375:Receptors, Interleukin-2 / Q000032:analysis; D011994:Recombinant Proteins / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000276:immunology* / Q000628:therapy
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins