Allostimulation-induced tumor cytotoxic cells: from mouse to man

Experimental tumors may express cell surface antigens which cross-react with alloantigens of normal allogeneic tissues(1). These may be H-2 or non-H-2 histocompatibility antigens and differentiation antigens(1-3). Because of this cross-reactivity animals immunized with allogeneic normal tissues bearing determinants shared by a syngeneic transplantable tumor acquire resistance to the tumor in vivo and lymphocytes specifically cytotoxic to syngeneic tumor cells in vitro. However, in similar experiments tumor cells which did not express detectable amounts of cross-reacting antigens were also rejected in syngeneic animals (mouse and rat) immunized with normal allogeneic tissues(4,5). In this instance the mechanism of antitumor rejection could not be clearly established(5). In other investigations allostimulation of the mouse lymphocytes in vitro generated cells cytotoxic against syngeneic tumor cells and allostimulation of human lymphocytes generated cells which killed autologous tumor cells(6-10). The mechanisms underlying these phenomena differ in detail but in each case the end result is the production of tumor-restricted cytotoxic cells. Here Giorgio Parmiani and his colleagues review these investigations and discuss the possible clinical utility of cytotoxic cells generated in this way.