Insulin-like growth factor II antisense oligonucleotide sequences and methods of using same to modulate cell growth

Abstract

This invention relates to oligonucleotides complementary to the IGF-II genes which modulate tumor cell growth in mammals This invention is also related to methods of using such compounds in inhibiting the growth of tumor cells in mammals This invention also relates to pharmaceutical compositions comprising a pharmaceutically acceptable excipient and an effective amount of a compound of this invention.

What is claimed:  
     
         1 . A method for inhibiting the growth of a human tumor comprising, administering to a human suspected of having the tumor an effective amount of an antisense oligonucleotide comprising from about 20 to 100 nucleotides comprising a sequence selected from the group consisting of SEQ ID NOs:17-31 in Table 2 under conditions such that the growth of the tumor is inhibited.  
     
     
         2 . The method according to  claim 1  wherein the oligonucleotide is nuclease resistant.  
     
     
         3 . The method according to  claim 1  further comprising the step of administering to the human a chemotherapeutic agent.  
     
     
         4 . A method for inhibiting the metastasis of a human tumor comprising, administering to a human suspected of having a metastatic tumor an effective amount of an antisense oligonucleotide from about 20 to 100 nucleotides comprising a sequence complementary to the 5′ untranslated region consisting of exons 4, 5 or 6 of human fetal IGF-II mRNA under conditions such that metastasis of the tumor is inhibited.  
     
     
         5 . The method according to  claim 4  further comprising the step of administering to the human a chemotherapeutic agent.  
     
     
         6 . The method according to  claim 4  wherein the oligonucleotide is nuclease resistant.  
     
     
         7 . The method according to  claim 4  wherein the oligonucleotide comprises a sequence selected from the group consisting of SEQ ID NOs:1-15.  
     
     
         8 . A method for inhibiting the metastasis of a human tumor comprising, administering to a human suspected of having a metastatic tumor an effective amount of an antisense oligonucleotide from about 20 to 100 nucleotides comprising a sequence selected from the group consisting of SEQ ID NOs:17-31 under conditions such that metastasis of the tumor is inhibited.  
     
     
         9 . The method according to  claim 8  further comprising the step of administering to the human a chemotherapeutic agent.  
     
     
         10 . The method according to  claim 9  wherein the oligonucleotide is nuclease resistant.  
     
     
         11 . The method according to  claim 4 , wherein the antisense oligonucleotide comprises from about 20 to about 50 nucleotides.