EFFECTIVE IMMUNE REJECTION OF ADVANCED METASTASIZED CANCER

A cellular cancer therapy is described with unique efficiency even in late-stage disease. in situ activated tumor-immune T cells, induced in allogeneic, tumor-resistant, MHC identical but superantigen different donor mice (B10.D2) could transfer strong graft-versus-leukemia (GvL) effects accompanied by only mild graft-versus-host (GvH) reactivity. Systemic immune cell transfer into 5 Gy irradiated DBA/2 mice bearing up to 4 week established syngeneic tumors and macrometastases led to m assive infiltration of tumor tissues by CD4 and CD8 donor T lymphocyte s. Upon interaction of immune CD4 donor T cells with host antigen pres enting cells in synergy with immune CD8 donor T cells attacking the tu mor cells directly, primary tumors (1.5 cm diameter) were encapsulated and rejected from the skin and liver metastases eradicated. For the f irst time, such adoptive cellular immunotherapy (ADI) was followed in individual live animals by P-31-NMR spectroscopy of primary tumors. An approximately 25,000 fold excess of metastatic tumor cells could be r ejected as revealed quantitatively by FACScan analysis of lacZ gene tr ansfected tumor cells.