Bispecific molecules for use in inducing antibody dependent effector cell-mediated cytotoxicity

Abstract

Bispecific molecules comprising a target cell specific ligand and an effector cell specific antibody or functional antibody fragment are disclosed.

1 . A bispecific molecule comprising: a target cell specific ligand and an effector cell specific antibody.  
     
     
         2 . A bispecific molecule of    claim 1   , wherein the ligand is an autocrine growth factor for a tumor cell.  
     
     
         3 . A bispecific molecule of    claim 2   , wherein the tumor cell is a human small-cell lung carcinoma cell.  
     
     
         4 . A bispecific molecule of    claim 3   , wherein the ligand binds to the gastrin-releasing peptide receptor.  
     
     
         5 . A bispecific molecule of    claim 4   , wherein the ligand is selected from the group consisting of bombesin and gastrin-releasing peptide, or analogues thereof.  
     
     
         6 . A bispecific molecule of    claim 1   , wherein the effector cell specific antobody binds the Fc receptor of an effector cell.  
     
     
         7 . A bispecific molecule of    claim 6   , wherein the effector cell specific antibody binds the Fcγ receptor at a site that is not inhibited by endogenous immunoglobulin.  
     
     
         8 . A bispecific molecule of    claim 7   , wherein the Fcγ receptor is selected from the group consisting of: FcγRI, FcγRII and FcγRIII.  
     
     
         9 . A bispecific molecule of    claim 8   , wherein the effector cell specific antibody is selected from the group consisting of: mAb22, mAb32, mAb44, mAb62 and mAb197.  
     
     
         10 . A bispecific molecule of    claim 1   , wherein the target cell specific ligand is bombesin or an analogue thereof and the effector cell specific antibody is a human FcγRI-specific monoclonal antibody.  
     
     
         11 . A target cell-specific effector cell for inducing an antibody dependent effector cell-mediated cytotoxicity against a target cell comprising: 
 (i) a target cell-specific ligand; and    (ii) an effector cell-specific antibody that is bound to an effector cell.    
     
     
         12 . A target cell-specific effector cell of    claim 11   , wherein the target cell is a tumor cell.  
     
     
         13 . A target cell-specific effector cell of    claim 12   , wherein the tumor cell is a human small-cell lung carcinoma cell.  
     
     
         14 . A target cell-specific effector cell of    claim 13   , wherein the target cell-specific ligand is an autocrine growth factor for the human small cell lung carcinoma cell.  
     
     
         15 . A target cell-specific effector cell of    claim 14   , wherein the target cell-specific ligand is selected from the group consisting of bombesin and gastrin-releasing peptide, and analogues thereof.  
     
     
         16 . A target cell-specific effector cell of    claim 1   , wherein the Fc receptor of the effector cell consisting of: FcγRI, FcγRII and FcγRIII.  
     
     
         17 . A target cell-specific effector cell of    claim 16   , wherein the effector cell-specific antibody is selected from the group consisting of: mAb22, mAb32, mAb44, mAb62 and mAb197.  
     
     
         18 . A method of inducing a specific antibody dependent effector cell-mediated cytotoxicity against a target cell, in a subject, comprising administering to the subject a bispecific molecule of    claim 1   ,    6   ,  9  or  10  in a pharmaceutically acceptable medium.  
     
     
         19 . A method of    claim 18   , wherein the a target cell is a tumor cell.  
     
     
         20 . A method of    claim 19   , wherein the tumor cell is a human small-cell lung carcinoma cell.  
     
     
         21 . A method for stimulating an immune response in a subject comprising administering to the subject a bispecific molecule specific ligand in a pharmaceutically acceptable carrier.  
     
     
         22 . A method of    claim 21    wherein the target cell specific ligand of the bifunctional molecule is an autocrine growth factor and the effector cell specific antibody is specific to an Fcγ receptor of an effector cell.  
     
     
         23 . A method of    claim 22    wherein the target cell specific ligand of the bifunctional molecule is selected from the group consisting of: insulin-like growth factor I, transferrin, vasoactive intestinal peptide, neurotensin, neuromedin B, neurophysin, tumor necrosis factor, transforming growth factor alpha, platelet derived growth factor, the transferin receptor and analogues thereof.  
     
     
         24 . A method of    claim 23    wherein the target cell specific ligand of the bifunctional molecule is selected from the group consisting of bombesin and gastrin releasing peptide or an analogue thereof.