The multicellular tumor spheroid model. II. Characterization of the primary allograft response in unsensitized mice.

The multicellular spheroid model previously has been used to characterize secondary allograft responses in sensitized mice. In this study multicellular spheroids of EMT6 mammary sarcoma were implanted into unsensitized allogeneic mice to assess sensitization, graft infiltration, and functional activities of host cells in a primary allograft response. During the first 5 days after implantation, the spheroids continued to grow similar to controls maintained in vitro. After 6 days the spheroids decreased in size, and recovery of clonogenic tumor cells fell markedly. Cytotoxic effector cells active in an in vitro 51Cr release assay were recoverable from the spheroids beginning at day 4 and reached a maximum at day 7. Lymphocytes and macrophages were present in the largest numbers at days 7 to 8. The predominant cytotoxic cell appears to be a T lymphocyte.