INDUCTION OF GRAFT VS TUMOR EFFECT IN A MURINE MODEL OF MAMMARY ADENOCARCINOMA

We have attempted to induce immune-mediated graft-vs.-tumor (GVT) effe cts against solid tumors, using a murine model of mammary adenocarcino ma derived from BALB/c(H-2(d)) mice. A cell line (4T1) isolated from t his tumor model was highly tumorigenic in syngeneic (BALB/c) or haplo- identical (BALB/c x C57B1/6)F-1 mice (F-1), was only partially tumorig enic in an H-(2)d congenic strain of mice (DBA/2) and was non-tumorige nic in a major histocompatible (MHC)-unrelated (H-2(b)) strain of mice (C57B1/6). 4T1 cells express class I MHC antigens and adhesion molecu les but do not express MHC class II antigens or B7-1 co-stimulatory mo lecules. Female BALB/c (H-2(d)) or F-1 (H-2(d/b)) mice were reconstitu ted with male bone marrow (BM) cells derived from minor histocompatibl e (MiHC) mismatched DBA (H-2(d)) donors or with MHC-mismatched C57B1/6 (H-2(b)) BM cells, respectively, 24 hr following lethal total body ir radiation. 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- o r MHC-incompatible with tumor cells were able to down-regulate the dev elopment of the primary tumor expressing host-type MHC alloantigens. T umor size in BM chimeras across MiHC or MHC antigens was significantly smaller than tumor size observed in normal BALB/c or F-1 controls. Th e GVT effect might be of help in improving immunotherapy for solid tum ors in humans. (C) 1997 Wiley-Liss, Inc.