Complex of alpha-fetoprotein and inducers of apoptosis for the treatment of cancer

Abstract

The invention relates to a composition comprising exogenous alpha-fetoprotein, a first compound reversibly bound to exogenous alpha-fetoprotein in vitro, and an unbound second compound wherein the first and second compound are anticancer drugs or combinations of anticancer drugs and wherein the second compound reversibly binds to recycled exogenous alpha-fetoprotein in vivo. A process for the butanol extraction of alpha-fetoprotein obtained from porcine blood and amniotic fluid during early embryogenesis and a process for the in vitro binding of alpha-fetoprotein and a first compound are also described. The invention also relates to a method of using these compositions to prevent, treat or inhibit a malignant neoplasm expressing an alpha-fetoprotein receptor.

1 . A composition comprising exogenous alpha-fetoprotein (AFP), a first compound reversibly bound to exogenous AFP in vitro, and a second compound wherein the first compound and the second compound are anticancer drugs and wherein the second compound reversibly binds to recycled, exogenous AFP in vivo.  
     
     
         2 . The composition of  claim 1  wherein the first compound and the second compound are the same anticancer drug.  
     
     
         3 . The composition of  claim 1  wherein the first compound and the second compound are different anticancer drugs.  
     
     
         4 . The composition of  claim 1  wherein the first compound comprises at least two anticancer drugs.  
     
     
         5 . The composition of  claim 1  wherein the second compound comprises at least two anticancer drugs.  
     
     
         6 . The composition of  claim 1  wherein the anticancer drugs induce apoptosis.  
     
     
         7 . The composition of  claim 6 , where the anticancer drugs are selected from the group consisting of atractyloside, thapsigargin, betulinic acid, CD 437, arsenic trioxide and lonidamine.  
     
     
         8 . The composition of any one of  claims 1  to  7  wherein the first compound and the second compound comprise separate dosage forms.  
     
     
         9 . A method of preventing, treating or inhibiting a malignant neoplasm, expressing an alpha-fetoprotein receptor (AFPR), the method comprising administering an effective amount of a composition comprising exogenous AFP, a first compound reversibly bound to exogenous AFP in vitro, and a second compound to a in need thereof, wherein the first compound and the second compound are anticancer drugs, and wherein the second compound reversibly binds to recycled, exogenous AFP in vivo.  
     
     
         10 . The method of  claim 9  wherein the first compound and the second compound are the same anticancer drug.  
     
     
         11 . The method of  claim 9  wherein the first compound and the second compound are different anticancer drugs.  
     
     
         12 . The method of  claim 9  wherein the first compound comprises at least two anticancer drugs.  
     
     
         13 . The method of  claim 9  wherein the second compound comprises at least two anticancer drugs.  
     
     
         14 . The method of  claim 9  wherein the anticancer drugs induce apoptosis.  
     
     
         15 . The method of  claim 14  wherein the anticancer drug are selected from the group consisting of atractyloside, thapsigargin, betulinic acid, CD 437, arsenic trioxide and lonidamine.  
     
     
         16 . The method of any one of  claims 9  to  15  wherein the first compound and the second compound are administered in separate dosage forms.  
     
     
         17 . A process for the butanol extraction of AFP comprising the following sequential steps: 
 collecting porcine blood and amniotic fluid during early embryogenesis;    separating the blood and the amniotic fluid into a supernatant and a precipitate;    collecting the supernatant resulting from step (b);    concentrating the supernatant resulting from step (c) to form a concentrated solution;    adding butanol to the concentrated solution resulting from step (d) to produce a 5-10% butanol solution;    stirring the butanol solution resulting from step (e);    separating the butanol solution resulting from step (f) into an upper non-aqueous phase and a lower aqueous phase; and    collecting the non-aqueous phase resulting from step (f) to produce a final solution having unbound AFP.    
     
     
         18 . A process for the in vitro binding AFP and a first compound comprising the following sequential steps: 
 mixing unbound AFP and a first compound;    incubating the unbound AFP and the first compound for about 10 minutes wherein the first compound reversibly binds to the unbound AFP to form an AFP-first compound mixture;    filtering the AFP-first compound mixture resulting from step (b) to form a filtrate having impurities and a retentate;    washing the retentate resulting from step (c) to form a washed retentate;    filtering the washed retentate resulting from step (d) to form a final solution; and    drying the final solution resulting from step (e) to form a dried, AFP-first compound product.