Antitumor activity and surface phenotypes of human glioma-infiltrating lymphocytes after in vitro expansion in the presence of interleukin 2.
The present study describes a method for in vitro expansion and characterization of antitumor-reactive lymphoid cells isolated from human malignant astrocytomas. Glioma-infiltrating lymphocytes were separated from 24 glioma specimens and cultured in medium containing interleukin 2 (50 to 2000 units/ml). Within 20 to 42 days after the initiation of culture, 20 of 24 cultures of glioma-derived lymphocytes expanded with a substantial increase in cell numbers, of at least 5 x 10(8) cells up to 5 x 10(9), with a simultaneous elimination of contaminating autologous glioma cells. The expanding glioma-derived lymphocytes consisted of 90 +/- 8% (SD) CD3+ T-cells including both CD4+ and CD8+ subpopulations. CD16 was expressed on 4 +/- 5% of the cells and three cultures studied exhibited 14% +/- 1 of Leu-19-positive cells. After 4 to 8 weeks of proliferation, interleukin 2 receptor expression decreased from 36 +/- 28% to less than 10% and the lymphocytes ceased to grow in all cultures. Glioma-derived effector lymphocytes could lyse almost all the autologous tumor targets as well as allogeneic glioma cells. The cytotoxic activity of long-term cultured peripheral blood lymphocytes obtained from the same patients appeared to be similar to that of glioma-derived lymphocytes in killing autologous tumor cells. In summary, glioma-derived lymphocytes expanded in bulk culture with high concentrations of interleukin 2 (2000 units/ml) consisted predominantly of T-lymphoblasts with the ability to kill autologous glioma cells. The tumor-infiltrating lymphocytes could be expanded to sufficient numbers for possible use in the adoptive immunotherapy of malignant gliomas.
Sawamura
Y
Y
Department of Neurosurgery, Hokkaido University School of Medicine, Sapporo, Japan.
Hosokawa
M
M
Kuppner
M C
MC
Kobayashi
H
H
Aida
T
T
Abe
H
H
de Tribolet
N
N
D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000032:analysis*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D005910:Glioma / Q000276:immunology*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D010641:Phenotype
D000954:Antigens, Surface; D007376:Interleukin-2