In vitro generation of cytolytic T cells against human melanoma cells overexpressing HDM2.
BACKGROUND
Previous experiments have shown that tumour-associated antigens can be exploited for a successful anti-tumour immunisation. Previous reports demonstrated that oncoprotein MDM2 (HDM2) contains two highly conserved MHC class I binding motifs, MDM2100 and MDM2441, and that dendritic cells (DC) presenting MDM2100 stimulate an effective CTL reaction against melanoma cells.


METHODS
In this study, we investigated the CTL-inducing capacity of autologous human dendritic cells pulsed with fragment HDM2441.


RESULTS
In vitro HDM2441-primed T lymphocytes revealed a strong proliferation activity, released Th-1-associated cytokines, and possessed an effective anti-tumour activity causing apoptosis in HDM2441-overexpressing melanoma cells. Cytotoxic assay demonstrated that in parallel to melanoma cells, up to 65% of primed Tcells also underwent apoptosis.


CONCLUSIONS
These data suggest that HDM2441 may be exploited for broad-spectrum DC-based trials against metastatic melanomas overexpressing HDM2, and point out that the efficacy of such immunotherapeutical approaches may be limited via T cell apoptosis.
Department of Immunology, Georg-August-University, 37075 Goettingen, Germany. asoruri@gwdg.de
Afsaneh
A
Soruri
Afshin
A
Fayyazi
Stefanie
S
Gangl
Christian
C
Griesinger
Christian A
CA
Albrecht
Thilo
T
Schlott
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000276:immunology; D001483:Base Sequence; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D008213:Lymphocyte Activation / Q000276:immunology; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D010446:Peptide Fragments / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051736:Proto-Oncogene Proteins c-mdm2; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology*
D009687:Nuclear Proteins; D010446:Peptide Fragments; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2