Specific eradication of micrometastases by transfer of tumour-immune T cells from major-histocompatibility-complex congenic mice.
DBA/2 (H-2d) mice bearing a transplanted highly metastatic lymphoma (ESb) in a state of widely disseminated disease could be successfully treated by a combination of surgery (removal of the local tumour), irradiation (5 Gy) and adoptive immunotherapy. The immunotherapy was achieved by transfer of anti-ESb-immune spleen cells from B10.D2 mice, which express the same major histocompatibility complex (MHC) molecules as DBA/2. In contrast, anti-ESb-immune cells from MHC-disparate C57BL/6 mice did not confer protective immunity. The B10.D2 anti-ESb-immune T cells contain two types of cytolytic specificity as detected by limiting-dilution analysis: (1) clones with specificity for the ESb-tumour-associated transplantation antigen (TATA) (at low frequency), and (b) clones with specificity for minor DBA/2 histocompatibility (H) antigens (at high frequency). Immune B10.D2 cells raised against different tumour lines or against TATA-ESb tumour variants did not confer the 100% protection seen with immune cells against ESb TATA+ cells. Finally we demonstrate that the allogeneic immune cells are more potent in terms of protective immunity than corresponding syngeneic immune cells. The data suggest that the strong graft-versus-leukemia effect with immune T cells from allogeneic MHC-identical but not from MHC-disparate mice was due to T cells with MHC-restricted specificity for an ESb-associated TATA. A graft-versus-host reactivity that developed much later and could not be prevented was most likely due to T cells sensitized against normal minor H antigens of the host. Our results are of potential relevance for allogeneic bone marrow transplantation and adoptive immunotherapy protocols.
Schirrmacher
V
V
Institut für Immunologie und Genetik, Deutsches Krebsforschungszentrum, Heidelberg, Federal Republic of Germany.
von Hoegen
P
P
Griesbach
A
A
Schild
H J
HJ
Zangemeister-Wittke
U
U
D000818:Animals; D015703:Antigens, CD; D002199:Capillary Permeability; D006087:Graft vs Host Reaction; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D007959:Lymphocyte Culture Test, Mixed; D008223:Lymphoma / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*
D015703:Antigens, CD