Specific eradication of micrometastases by transfer of tumour-immune T cells from major-histocompatibility-complex congenic mice |
| |
Authors: | Volker Schirrmacher Paul von Hoegen Andreas Griesbach Hans-Jörg Schild Uwe Zangemeister-Wittke |
| |
Institution: | (1) Institut für Immunologie und Genetik, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, W-6900 Heidelberg, Germany;(2) Present address: Medical Center, Stanford University, 94 305 Stanford, California, USA |
| |
Abstract: | Summary 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. |
| |
Keywords: | Leukemia Immunotherapy Micrometastases |
本文献已被 SpringerLink 等数据库收录! |
|