Adoptive immunotherapy with peripheral blood lymphocytes cocultured in vitro with autologous tumor cells and interleukin-2.
A clinical trial of adoptive immunotherapy was carried out with peripheral blood lymphocytes (PBL), cocultured in vitro with autologous tumor cells and interleukin-2 (IL-2), in 14 patients with advanced melanoma. PBL from these patients were cocultured with irradiated autologous tumor cells for 7 days, which was followed by expansion in IL-2-containing medium. These lymphocytes were returned to the patient along with intravenous IL-2 at doses up to 2 x 10(6) IU m-2 day-1. A dose of 300 mg/m2 cyclophosphamide was administered to each patient intravenously 4 days prior to each treatment. Following coculture, the lymphocytes were primarily CD3+ T cells and they expressed varied degrees of cytotoxicity against autologous melanoma cells. In 9 patients the activated cells were at least 80% CD4+ and in 2 cases they were mostly CD8+. Some of the activated cells exhibited suppressor or helper activity in a functional regulatory coculture assay. No major therapeutic response was observed in this study. Minor responses were observed in 2 patients. Toxicities were those expected from the IL-2 dose administered.
Department of Medicine, University of Connecticut Health Center, Farmington 06030.
J R
JR
Sporn
M T
MT
Ergin
G R
GR
Robbins
R G
RG
Cable
H
H
Silver
B
B
Mukherji
D000328:Adult; D000368:Aged; D002460:Cell Line; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000628:therapy*; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003520:Cyclophosphamide