A LYMPHOCYTE-ACTIVATING MONOCLONAL-ANTIBODY INDUCES REGRESSION OF HUMAN TUMORS IN SEVERE COMBINED IMMUNODEFICIENT MICE

Monoclonal antibodies were raised against Daudi B-lymphoblastoid cell line membranes, An mAb (BAT) was selected for its ability to stimulate human and murine lymphocyte proliferation, BAT induced cytotoxicity i n human and murine lymphocytes against natural killer cell-sensitive a nd -resistant tumor cell lines, A single intravenous administration of BAT to mice that had been inoculated with various murine tumors (e,g, , B16 melanoma, 3LL carcinoma, and methylcholanthrene fibrosarcoma) re sulted in striking antitumor effects as manifested by complete tumor r egression and prolonged survival of the treated mice, BAT exhibited a diminished but significant antitumor effect in athymic nude mice, whic h are deficient in T lymphocytes, and in beige mice, which are deficie nt in NK cells, Furthermore, selective depletion of T or NK cells in m ice reduced the response to the antitumor effect of BAT, These data in dicate a dual role for T and NK cells in mediating the antitumor activ ity of BAT, We report here on the antitumor activity of BAT mAb on hum an tumor xenografts in mice, BAT demonstrated an antitumor effect in n ude mice bearing human colon carcinoma (HT29) xenografts, It failed, h owever, to inhibit established lung metastases in severe combined immu nodeficient (SCID) mice that had been inoculated (i,v,) with SK28 huma n melanoma, Engraftment of human lymphocytes into SCID mice bearing hu man melanoma xenografts rendered them responsive to the antitumor effe ct of BAT, The efficacy of BAT in the regression of human tumors by ac tivation of human lymphocytes indicates its potential clinical use.