Compositions for inducing immune responses specific to globo h and ssea3 and uses thereof in cancer treatment

Abstract

An immune composition containing Globo H or its fragment (e.g., SSEA3) and an adjuvant, e.g., α-GalCer, for eliciting immune responses against Globo H or its fragment and uses thereof in cancer treatment. Also disclosed is a method of treating cancer by inhibiting the activity of one of FUT1 and FUT2, both of which involve in Globo H biosynthesis.

1 . An immune composition comprising a glycan and α-galactosyl-ceramide (α-GalCer), wherein the glycan is Globo H or a fragment thereof. 
   
   
       2 . The immune composition of  claim 1 , wherein the glycan is Globo H. 
   
   
       3 . The immune composition of  claim 1 , wherein the glycan is SSEA3. 
   
   
       4 . The immune composition of  claim 1 , wherein the glycan or its fragment is conjugated with Keyhole Limpet Hemocyanin (KLH). 
   
   
       5 . An immune composition comprising SSEA3 and an adjuvant. 
   
   
       6 . A method of treating cancer, comprising administering to a subject in need thereof an effective amount of the immune composition of  claim 1 . 
   
   
       7 . The method of  claim 6 , wherein the cancer is selected from the group consisting of breast cancer, prostate cancer, ovarian cancer, and lung cancer. 
   
   
       8 . The method of  claim 7 , wherein the cancer is breast cancer. 
   
   
       9 . The method of  claim 6 , wherein the glycan is Globo H and the immune composition elicits an immune response against Globo H. 
   
   
       10 . The method of  claim 6 , wherein the glycan is SSEA3 and the immune composition elicits an immune response against SSEA3. 
   
   
       11 . A method of treating cancer, comprising administering to a subject in need thereof an effective amount of the immune composition of  claim 5 . 
   
   
       12 . The method of  claim 11 , wherein the cancer is selected from the group consisting of breast cancer, lung cancer, liver cancer, oral cancer, stomach cancer, colon cancer, nasopharynx cancer, skin cancer, kidney cancer, brain tumor, prostate cancer, ovarian cancer, cervical cancer, and bladder cancer. 
   
   
       13 . The method of  claim 12 , wherein the cancer is breast cancer. 
   
   
       14 . A method of producing an antibody specific to Globo H or its fragment, comprising
 administering to a non-human mammal an effective amount of a composition containing Globo H or a fragment thereof and α-galactosyl-ceramide (α-GalCer) to induce production of an antibody that binds to Globo H or its fragment, and   isolating the antibody.   
   
   
       15 . The method of  claim 14 , wherein the composition contains Globo H. 
   
   
       16 . The method of  claim 14 , wherein the composition contains SSEA3. 
   
   
       17 . A method of treating cancer, comprising administering to a subject in need thereof an effective amount of a first agent that inhibits the activity of 2-fucosyltransferase 1 (FUT1) or 2-fucosyltransferase 2 (FUT2), wherein the agent is an antibody that blocks interaction between FUT1 or FUT2 and its substrate or an interfering RNA that suppresses expression of FUT1 or FUT2. 
   
   
       18 . The method of  claim 17 , wherein the first agent is a small interfering RNA (siRNA). 
   
   
       19 . The method of  claim 18 , wherein the siRNA is siFUT1 or siFUT2. 
   
   
       20 . The method of  claim 17 , wherein the first agent inhibits the activity of FUT1 and the subject is further administered with an effective amount of a second agent that inhibits the activity of FUT2, the second agent being an antibody that blocks interaction between FUT2 and its substrate or an interfering RNA that suppresses expression of FUT2. 
   
   
       21 . The method of  claim 20 , wherein the first and second agents are siRNAs. 
   
   
       22 . The method of  claim 21 , wherein the first and second agents are siFUT1 and siFUT2, respectively. 
   
   
       23 . The method of  claim 17 , wherein the cancer is breast cancer.