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 in human and murine lymphocytes against natural killer cell-sensitive and -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) resulted in striking antitumor effects as manifested by complete tumor regression and prolonged survival of the treated mice. BAT exhibited a diminished but significant antitumor effect in athymic nude mice, which are deficient in T lymphocytes, and in beige mice, which are deficient in NK cells. Furthermore, selective depletion of T or NK cells in mice reduced the response to the antitumor effect of BAT. These data indicate a dual role for T and NK cells in mediating the antitumor activity of BAT. We report here on the antitumor activity of BAT mAb on human tumor xenografts in mice. BAT demonstrated an antitumor effect in nude mice bearing human colon carcinoma (HT29) xenografts. It failed, however, to inhibit established lung metastases in severe combined immunodeficient (SCID) mice that had been inoculated (i.v.) with SK28 human melanoma. Engraftment of human lymphocytes into SCID mice bearing human melanoma xenografts rendered them responsive to the antitumor effect of BAT. The efficacy of BAT in the regression of human tumors by activation of human lymphocytes indicates its potential clinical use.
Hardy
B
B
Felsenstein Medical Research Center, Rabin Medical Center, Belinson Campus, Petah Tikva 49100, Israel.
Kovjazin
R
R
Raiter
A
A
Ganor
N
N
Novogrodsky
A
A
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D002277:Carcinoma / Q000276:immunology / Q000628:therapy; D002460:Cell Line; D003110:Colonic Neoplasms / Q000276:immunology / Q000628:therapy*; D005260:Female; D005354:Fibrosarcoma / Q000139:chemically induced / Q000276:immunology / Q000628:therapy; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology / Q000556:secondary / Q000628:therapy; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D017710:Lymphocyte Transfusion; D008545:Melanoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008546:Melanoma, Experimental / Q000276:immunology / Q000628:therapy; D008748:Methylcholanthrene; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016513:Mice, SCID; D013154:Spleen / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D008748:Methylcholanthrene