Induction and large-scale expansion of CD8+ tumor specific cytotoxic T lymphocytes from peripheral blood lymphocytes by in vitro stimulation with CD80-transfected autologous melanoma cells.
Human melanoma cell lines may induce a specific T cell response against tumor cells in vitro. However, after repeated restimulation with autologous tumor cells, expansion of CTL is limited and often apoptosis of the T cells occurs. In order to improve conditions inducing primary T cell responses and thus allowing further expansion of tumor specific T cells for an adoptive transfer, we transfected human melanoma cells with the B7.1 gene (CD80), known to be a potent costimulatory molecule for T cell activation. CD80 expression on melanoma cells resulted in improved primary T cell activation, especially of CD8+ T cells. Furthermore, restimulation with CD80+ tumor cells gave rise to long term proliferating CD8+ T cell lines demonstrating an 100-fold expansion of T cells compared to the 20-30-fold increased numbers obtained with the controls (parental tumor cells +/- anti-CD28). T cells stimulated with CD80+ melanoma cells were found to display a MHC class I-restricted cytotoxic activity against the autologous tumor cells. In conclusion, these studies demonstrate the requirement of costimulation in generating large numbers of tumor specific T cells in vitro that may be used for an adoptive transfer in tumor immunotherapy.
Mackensen
A
A
Dept. of Hematology & Oncology, Univ. of Regensburg, Franz-Joseph-Strauss-Allee, 11, D-93042 Regensburg, Allemagne.
Wittnebel
S
S
Veelken
H
H
Noppen
C
C
Spagnoli
G C
GC
Lindermann
A
A
D019264:Adoptive Transfer; D018122:B7-1 Antigen / Q000235:genetics*; D001483:Base Sequence; D002455:Cell Division / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008545:Melanoma / Q000276:immunology* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000276:immunology; D014162:Transfection
D018122:B7-1 Antigen; D017931:DNA Primers; D018664:Interleukin-12