Retargeting of T-cell-receptor gamma/delta+ lymphocytes against tumor cells by bispecific monoclonal antibodies. Induction of cytolytic activity and lymphokine production.
We have recently selected MAbs specific for different molecular forms of the TCR gamma/delta (expressed by distinct cell subsets), able to activate TCR gamma/delta+ cells. Two of these reagents (G1 and A13) were used for the construction of bispecific MAbs in conjunction with a MAb (Mov19) directed to ovarian carcinoma cells, using the hybrid hybridoma technique. The G1-derived bispecific MAb GM33.9 efficiently induced lysis of Mov19+ ovarian carcinoma cell lines (IGROVI and SW626) by G1+ clones in a 4-hr 51Cr-release assay. On the other hand, it was ineffective when Mov19- target cells were used. Comparable results were obtained with the A13-derived AM18.4 bispecific MAb when A13+ clones were used as effector cells. Bispecific MAbs were also able to induce secretion of IL-2 and TNF-alpha by TCR gamma/delta+ clones when Mov19+ target cells were present.
Ferrini
S
S
Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Prigione
I
I
Mammoliti
S
S
Colnaghi
M I
MI
Menard
S
S
Moretta
A
A
Moretta
L
L
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000276:immunology*; D002277:Carcinoma / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008222:Lymphokines / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000276:immunology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D008222:Lymphokines; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D013755:Tetradecanoylphorbol Acetate