ALLOGENEIC CELL THERAPY FOR A MURINE MAMMARY-CARCINOMA

The effect of allogeneic cell therapy on tumor growth was studied in a murine model of mammary carcinoma (4T1) as an experimental model of s olid tumors in humans. i.v. inoculation of 4T1 (H-2(d)) cells into syn geneic mice [BALB/c or (BALB/cXC57BL/6)F-1] (F-1) carrying the H-2(d) histocompatible antigens results in tumor colonies in the lungs that f inally cause the death of all of the mice. Sublethally irradiated F-1 mice were inoculated with 4T1 cells to simulate minimal residual disea se and with immunocompetent splenocytes derived from naive donors of F -1 (syngeneic), BALB/c (syngeneic to the tumor but semiallogeneic to t he host), or C57BL/6 (allogeneic to the tumor and semiallogeneic to th e host) mice. The survival of F-1 tumor-bearing mice that were treated with allogeneic C57BL/6 splenocytes was significantly prolonged (P < 0.02) compared with hosts given F-1 or BALB/c-derived splenocytes that are syngeneic to 4T1 tumor cells. Adoptive transfer of lung cells tha t were isolated from F-1 primary mice inoculated with 4T1 cells and sy ngeneic BALB/c or F-1 splenocytes led to local tumor growth and death in secondary recipients. In contrast, only 1 of 22 secondary recipient s developed tumors when inoculated with lung cells derived from F-1 mi ce given allogeneic C57BL/6 splenocytes. All of the 21 secondary hosts survived disease-free for a follow-up time of >200 days. These result s indicate that immunocompetent cells allogeneic to the mammary carcin oma cells were able to inhibit tumor development in the primary hosts and to prevent tumor growth in the adoptive recipients, which suggests that allogeneic cell therapy may be an efficient antitumor tool to er adicate minimal residual disease in human solid tumors.