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

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Abstract
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 (4TI) isolated from this tumor model was highly tumorigenic in syngeneic (BALB/c) or haplo‐identical (BALB/c × 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). 4T1 cells express class I MHC antigens and adhesion molecules but do not express MHC class II antigens or B7‐I 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 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 tumour 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 F1 controls. The GVT effect might be of help in improving immunotherapy for solid tumors in humans. Int. J. Cancer, 71:59–63, 1997.