Active immunization of metastatic melanoma patients with interleukin-2-transduced allogeneic melanoma cells: evaluation of efficacy and tolerability.
From January 1994 to July 1996 we immunized metastatic melanoma patients with HLA-A2-compatible, interleukin-2 (IL-2)-secreting, immunogenic melanoma lines in an attempt to induce a systemic reaction that might also affect distant melanoma lesions. Twelve patients (6 male and 6 female) aged from 28 to 72 years, affected with visceral and/or subcutaneous (s.c.) melanoma metastases, were treated. Two different HLA-A2+ melanoma lines were transduced with the human IL-2 gene (14932/IL-2 and 1B6/IL-2) and used as vaccine. Two groups of 4 patients each were injected s.c. with 5 x 10(7) and 15 x 10(7) irradiated 14932/IL-2 melanoma cells respectively, whereas a third group received 5 x 10(7) cells of the second line (1B6/IL-2). All patients received the vaccine on days 1, 13, 26; if no progression was evident, further immunizations were administered at monthly intervals. All patients were assessable for clinical response after at least three injections of the vaccine. In 4 cases a stabilization of disease lasting from 2 to 6 months was observed: in 2 of them a mixed type of response to treatment was noted with simultaneous evidence of regressing and non-responding lesions in the same patients. No signs of clinical response were found in the remaining patients. Nine patients died of disease between 3 and 24 months after the onset of therapy, whereas 3 were alive 3 months after the end of therapy. The local and systemic side-effects of treatment were mild. These results indicate that vaccination with cells bearing the appropriate antigens and releasing IL-2 locally can produce weak clinical responses, but also indicate that better results may be achieved through modifications of the vaccine, the schedule of immunization and/or a more appropriate selection of patients.
Belli
F
F
Division of Surgical Oncology B, Istituto Nazionale Tumori, Milan, Italy.
Arienti
F
F
Sulé-Suso
J
J
Clemente
C
C
Mascheroni
L
L
Cattelan
A
A
Santantonio
C
C
Gallino
G F
GF
Melani
C
C
Rao
S
S
Colombo
M P
MP
Maio
M
M
Cascinelli
N
N
Parmiani
G
G
Sanatonio
C
C
D000328:Adult; D000368:Aged; D017690:Cell Transplantation / Q000379:methods / Q000592:standards*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015789:HLA-A2 Antigen / Q000032:analysis / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D016233:Immunotherapy, Active / Q000592:standards*; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology* / Q000628:therapy*; D012983:Soft Tissue Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy; D013997:Time Factors; D014161:Transduction, Genetic; D014184:Transplantation, Homologous / Q000379:methods / Q000592:standards; D014407:Tumor Cells, Cultured
D015789:HLA-A2 Antigen; D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor