Suppression of normal and neoplastic human T cells with unconjugated monoclonal antibodies in SCID mouse chimeras.
The aim of this study was to establish a preclinical in vivo model to evaluate the suppressive effect of unconjugated anti-human T (CD3, 5, 7)-cell monoclonal antibodies (mAb) of mouse IgG2a or rat IgG2b isotype. Therefore, severe combined immunodeficient (SCID) mice were transplanted with human peripheral blood lymphocytes (PBL) of healthy donors (hu-PBL-SCID) or with neoplastic T cells of the human T-ALL cell line Jurkat. In preselected hu-PBL-SCID mice with substantial T cell chimerism single antibody injection caused prompt suppression of circulating human T lymphocytes within 2 days followed by occasional T cell recovery during the following weeks. Furthermore, antibody-mediated T cell suppression was measured by prolonged survival of SCID mice that had been injected with Jurkat cells preadapted to cause 100% mortality within 40 days. Injection of preadapted Jurkat cells caused fatal metastasis in lymphoid as well as non-lymphoid organs. The progression of leukemic cells was successfully suppressed when cells and anti-T cell mAb were given i.p. In contrast to control mice, tumor mortality of antibody-treated animals was delayed or completely suppressed. We conclude that SCID mice with reproducible human T cell chimerism are a relevant animal model to test the suppressive effect of anti-human T cell mAb in preclinical studies.
GSF-Institut für Immunologie Marchioninistr 25, Munich, Germany.
U
U
Zengerle
G
G
Hoffmann-Fezer
R
R
Schuh
S
S
Thierfelder
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D008212:Lymphocyte Depletion; D051379:Mice; D016513:Mice, SCID; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000637:transplantation; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G