Induction of graft vs. tumor effect in a murine model of mammary adenocarcinoma

✍ Scribed by S. Morecki; Y. Moshel; Y. Gelfend; T. Pugatsch; S. Slavin

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: French
• Weight: 112 KB
• Volume: 71
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19970328)71:1<59::aid-ijc11>3.0.co;2-4

✦ Synopsis

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-2 d ) mice. A cell line (4T1) isolated from this tumor model was highly tumorigenic in syngeneic (BALB/c) or haplo-identical (BALB/c 3 C57Bl/6)F 1 mice (F 1 ), was only partially tumorigenic in an H-2 d congenic strain of mice (DBA/2) and was non-tumorigenic in a major histocompatible (MHC)-unrelated (H-2 b ) strain of mice (C57Bl/6). 4T1 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-2 d ) or F 1 (H-2 d/b ) mice were reconstituted with male bone marrow (BM) cells derived from minor histocompatible (MiHC)-mismatched DBA (H-2 d ) donors or with MHC-mismatched C57Bl/6 (H-2 b ) BM cells, respectively, 24 hr following lethal total body irradiation. Recipient mice carrying MiHC-or MHC-mismatched donor cells were inoculated with 4T1 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-type MHC alloantigens. Tumor size in BM chimeras across MiHC or MHC antigens was significantly smaller than tumor size observed in normal BALB/c or F 1 controls. The GVT effect might be of help in improving immunotherapy for solid tumors in humans.