Human T Cells Targeted with Hetero‐cross‐linked Antibodies Prevent Tumor Growth in Nude Mice

When human cytotoxic T lymphocytes (CTL) are coated with anti-T3, crosslinked to antitarget cell antibody (anti-T3 x antitarget), they lose their natural specificity and become cytotoxic for cells recognized by the antitarget cell antibody.' Fresh human peripheral blood T cells (PBT) will mediate such targeted lysis, and all in uitro cytotoxic activity resides in the T8+ subset.2 These cells, when treated with anti-T3 x antitumor, will specifically lyse, in uitro, cultured or fresh tumor cells, but not fresh cells from normal tissue.' We have tested targeted PBT for the ability to prevent subcutaneous tumor growth of the LS174T human colon adenocarcinoma line in a Winn-type4 tumor neutralization assay in nude mice.s PBT, coated with anti-T3(Fab) x 315F6(Fab) (315F6 is an antitumor antibody that cross-reacts on LS174T), prevent the growth of LS174T tumors at less than 1 : I T cell : tumor cell ratios (Table I , rows, 4-6). Specificity controls established that an antitumor antibody must be physically linked to anti-T3 in order for tumor neutralization to occur.5 Although Leu-1 1 + PBL mediate substantial antibody-independent, NK-like activity against LS174T cells in uitro, these cells are ineffective at preventing tumor growth in uiuo (TABLE 1 , rows I and 3). Removal of the T8+ subset of cells totally abolishes in uirro cytotoxicity, but has little effect on the tumor neutralizing activity of targeted PBT (TABLE I , rows 4-6 and 8-10). Further studies (TABLE 2) showed that all of the tumor-neutralizing activity resides in cells expressing either T4 or T8 (TABLE 2, rows 9 and lo), with each subset exhibiting some tumor-neutralizing activity (rows 5-8). These studies show that targeted T cells are highly effective in preventing the establishment of at least one type of tumor. The studies also lay the groundwork for experiments involving the elimination of established tumors.