Bispecific antibodies increase T-cell stimulatory capacity in vitro of human autologous virus-modified tumor vaccine.
The production and functional testing of two new bispecific (bs) hybrid antibodies [Abs; bs Ab hemagglutinin-neuraminidase (HN) x CD3 and bs Ab HN x CD28] designed for cancer vaccine modification are described. They allow distinct modifications of the human tumor cell vaccine ATV-NDV, an autologous tumor cell vaccine already modified by infection with Newcastle disease virus. The bs Abs use the viral HN molecule as a common foreign anchoring molecule for attachment to the tumor cells and allow the introduction of anti-CD3 or anti-CD28 T-cell-stimulatory molecules. The bs Abs attached to tumor target cells were able to cross-link CTL effector cells and up-regulate T-cell activation markers on autologous cancer patient-derived CD4 and CD8 T lymphocytes. This strategy of combining a cellular vaccine with a bs Ab is highly specific, quick, and economical and has broad-range applications. Five ng or less of target cell-bound bs Ab HN x CD28 were effective at augmenting T-cell-mediated antitumor cytotoxicity.
Haas
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C
Division of Cellular Immunology, German Cancer Research Center, Heidelberg.
Strauss
G
G
Moldenhauer
G
G
Iorio
R M
RM
Schirrmacher
V
V
D018033:Antibodies, Bispecific / Q000494:pharmacology*; D015703:Antigens, CD / Q000032:analysis; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines; D002460:Cell Line; D003110:Colonic Neoplasms; D005720:Gamma Rays; D015707:HN Protein / Q000276:immunology*; D006801:Humans; D006825:Hybridomas; D016130:Immunophenotyping; D007167:Immunotherapy / Q000379:methods; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D009522:Newcastle disease virus; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D018033:Antibodies, Bispecific; D015703:Antigens, CD; D018106:CD28 Antigens; D017252:CD3 Complex; D019496:Cancer Vaccines; D015707:HN Protein