A novel tumour model system for the study of long-term protective immunity and immune T cell memory.
We present a novel non-transgenic system to be used for studies on anti-tumour adoptive immunotherapy (ADI) and long-term T cell memory. Tumour-reactive donor immune cells against lacZ-transfected syngeneic tumour cells (ESbL-Gal) were generated from a naíve T cell repertoire in DBA/2 mice by a well-established priming/restimulation protocol, and transferred to tumour-inoculated athymic nu/nu mice. The donor immune cells efficiently mediated protective anti-tumour immunity involving both CD4(+) and CD8(+) T cells, and anti-metastatic effects were stronger in 4.5 Gy pre-irradiated than in non-irradiated tumour-inoculated hosts. Long-term persistence of beta-galactosidase (Gal)-specific T cells was shown ex vivo by tetramer staining of CD8(+) T cells specific for an immunodominant Gal epitope. Resistance of treated nu/nu mice against tumour rechallenge revealed the existence of long-term protective immune memory.
Tumour Immunology Program, Division of Cellular Immunology, German Cancer Research Centre, Im Neuenheimer Feld 280, D-69120, Heidelberg, Germany.
Yolanda D
YD
Mahnke
Volker
V
Schirrmacher
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines; D003601:Cytotoxicity Tests, Immunologic; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000276:immunology*; D016219:Immunotherapy, Adoptive / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014611:Vaccination; D014916:Whole-Body Irradiation
D019496:Cancer Vaccines