Compositions and Methods for Treatment of Neoplastic Disease

Abstract

The present invention comprises the use of sickle cells or sickle cell precursors loaded with a therapeutic agent that localize in tumors and induce a tumoricidal response.

1 - 23 . (canceled) 
     
     
         24 . A method of treating a subject with a primary or metastatic carcinoma of the lung or pleura with or without pleural effusion comprising administering to said subject in need thereof parenterally by infusion or injection a tumoricidally effective amount of a composition consisting of:
 (i) a native staphylococcal enterotoxin or streptococcal pyrogenic exotoxin protein which native protein:
 (a) has the biological activity of stimulating T cell mitogenesis via a T cell receptor vβ region; or 
   (ii) a biologically active homologue or fragment of a native staphylococcal enterotoxin or streptococcal pyrogenic exotoxin, which homologue or fragment:
 (a) has the biological activity of stimulating T cell mitogenesis via a T cell receptor vβ region and 
 (b) has sequence homology characterized as a z value exceeding 10 when the sequence of the homologue or said fragment is compared to the sequence of a native staphylococcal enterotoxin or a native streptococcal pyrogenic exotoxin, determined by FASTA analysis using gap penalties of-12 and -2, Blosum 50 matrix and Swiss-PROT or PR database; or 
   (iii) a biologically active fusion protein having said biological activity and said sequence homology, comprising
 (A) said homologue, 
 (B) a native staphylococcal enterotoxin, 
 (C) a native streptococcal pyrogenic exotoxin, or 
 (D) a biologically active fragment of said homologue, said native enterotoxin or said native exotoxin, fused to a peptide or polypeptide fusion partner, wherein said fusion partner is a peptide or polypeptide costimulatory molecule selected from a group consisting of OX-40 ligand or 4-1BB ligand. 
   
     
     
         25 . The method of  claim 24  wherein said fusion protein is further fused to a ligand specific for receptors selectively or preferentially expressed on tumor cells or an antibody or antibody fragment specific for tumor cells, tumor vasculature or tumor stroma. 
     
     
         26 . The method according to  claim 24  or wherein the native staphylococcal enterotoxin and streptococcal pyrogenic exotoxin is selected from a group comprising staphylococcal enterotoxin A, staphylococcal enterotoxin A, staphylococcal enterotoxin A, staphylococcal enterotoxin B, staphylococcal enterotoxin CI, staphylococcal enterotoxin C2, staphylococcal enterotoxin C3, staphylococcal enterotoxin D, staphylococcal enterotoxin E, Toxic Shock Syndrome Toxin-1, staphylococcal enterotoxin G, staphylococcal enterotoxin H, staphylococcal enterotoxin I, staphylococcal enterotoxin J, staphylococcal enterotoxin K, staphylococcal enterotoxin L, staphylococcal enterotoxin M, streptococcal pyrgogenic exotoxin A, streptococcal pyrogenic exotoxin B, streptococcal pyrgogenic exotoxin C, staphylococcal superantigen A, streptococcal pyrgogenic exotoxin G, streptococcal pyrgogenic exotoxin H, streptococcal mitogenic exotoxin z. 
     
     
         27 . The method according to  claim 25  or wherein the native staphylococcal enterotoxin and streptococcal pyrogenic exotoxin is selected from a group comprising staphylococcal enterotoxin A, staphylococcal enterotoxin A, staphylococcal enterotoxin A, staphylococcal enterotoxin B, staphylococcal enterotoxin CI, staphylococcal enterotoxin C2, staphylococcal enterotoxin C3, staphylococcal enterotoxin D, staphylococcal enterotoxin E, Toxic Shock Syndrome Toxin-1, staphylococcal enterotoxin G, staphylococcal enterotoxin H, staphylococcal enterotoxin I, staphylococcal enterotoxin J, staphylococcal enterotoxin K, staphylococcal enterotoxin L, staphylococcal enterotoxin M, streptococcal pyrgogenic exotoxin A, streptococcal pyrogenic exotoxin B, streptococcal pyrgogenic exotoxin C, staphylococcal superantigen A, streptococcal pyrgogenic exotoxin G, streptococcal pyrgogenic exotoxin H, streptococcal mitogenic exotoxin z. 
     
     
         28 . The method according to  claim 24  wherein the tumoricidally effective amount of the said staphylococcal entertoxin and streptococcal pyrogenic exotoxin compositions comprise administering said tumoricidal amount of said compositions to said subjects parenterally, intratumorally, intrathecally, intraperitoneally, intrapleurally by infusion or injection. 
     
     
         29 . The method according to  claim 25  wherein the tumoricidally effective amount of the said staphylococcal entertoxin and streptococcal pyrogenic exotoxin compositions comprise administering said tumoricidal amount of said compositions to said subjects parenterally, intratumorally, intrathecally, intraperitoneally, intrapleurally by infusion or injection.