Induction of graft vs. tumor effect in a murine model of mammary adenocarcinoma.
We have attempted to induce immune-mediated graft-vs.-tumor (GVT) effects against solid tumors, using a murine model of mammary adenocarcinoma derived from BALB/c(H-2d) mice. A cell line (4Tl) isolated from this tumor model was highly tumorigenic in syngeneic (BALB/c) or haplo-identical (BALB/c x C57B1/6)F1 mice (F1), was only partially tumorigenic in an H-2d congenic strain of mice (DBA/2) and was non-tumorigenic in a major histocompatible (MHC)-unrelated (H-2b) strain of mice (C57B1/6). 4Tl cells express class I MHC antigens and adhesion molecules but do not express MHC class II antigens or B7-1 co-stimulatory molecules. Female BALB/c (H-2d) or F1 (H-2d/b) mice were reconstituted with male bone marrow (BM) cells derived from minor histocompatible (MiHC)-mismatched DBA (H-2d) donors or with MHC-mismatched C57B1/6 (H-2b) BM cells, respectively, 24 hr following lethal total body irradiation. Recipient mice carrying MiHC- or MHC-mismatched donor cells were inoculated with 4Tl cells 2-3 months following BM reconstitution. Chimeras reconstituted with allogeneic donor cells that were MiHC- or MHC-incompatible with tumor cells were able to down-regulate the development of the primary tumor expressing host-ype MHC alloantigens. Tumor size in BM chimeras across MiHC or MHC antigens was significantly smaller than tumor size observed in normal BALB/c or F1 controls. The GVT effect might be of help in improving immunotherapy for solid tumors in humans.
Morecki
S
S
Department of Bone Marrow Transplantation, Hadassah University Hospital, Jerusalem, Israel.
Moshel
Y
Y
Gelfend
Y
Y
Pugatsch
T
T
Slavin
S
S
D000230:Adenocarcinoma / Q000276:immunology*; D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D002678:Chimera / Q000276:immunology*; D005260:Female; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D015778:Minor Histocompatibility Antigens / Q000276:immunology; D009368:Neoplasm Transplantation; D015996:Survival Rate
D015778:Minor Histocompatibility Antigens