Iga fc-folate conjugates, pharmaceutical compositions and methods to treat cancer

Abstract

IgA-based Fc-folate conjugates as a treatment for cancer are provided. The conjugates utilize only the Fc portion of IgA to target its receptor on neutrophils (FcαR1) to elicit antibody-dependent cellular-cytotoxicity (ADCC).

What is claimed is: 
     
         1 . A complex comprising:
 a folate receptor alpha (FRA)-expressing cancer cell from a subject; and   bound thereto, a conjugate comprising:
 an Fc portion of an IgA antibody, wherein said Fc portion comprises a CH2 domain and a CH3 domain but does not comprise a hinge region; and 
 folate or a folate analog. 
   
     
     
         2 . The complex of  claim 1 , wherein the conjugate further comprises a linker. 
     
     
         3 . The complex of  claim 2 , wherein the linker is a peptide linker. 
     
     
         4 . The complex of  claim 2 , wherein the linker is a non-peptide linker. 
     
     
         5 . The complex of  claim 1 , wherein the Fc portion is a variant Fc. 
     
     
         6 . The complex of  claim 1 , wherein the Fc portion is a variant Fc and the conjugate comprises folate. 
     
     
         7 . The complex of  claim 1 , wherein the Fc portion is a variant Fc and the conjugate comprises a folate analog. 
     
     
         8 . The complex of  claim 1 , wherein the Fc fragment consists of a CH2/CH3 region from an IgA antibody. 
     
     
         9 . The complex of  claim 1 , which is in vitro, or in vivo in the subject. 
     
     
         10 . A method of inducing antibody-dependent cell-mediated cytotoxicity (ADCC), against folate receptor alpha (FRA)-expressing cancer cells, in neutrophils in a subject, the method comprising:
 administering to the subject a therapeutically effective amount of a conjugate comprising:
 an Fc portion of an IgA antibody, wherein said Fc portion comprises a CH2 domain and a CH3 domain but does not comprise a hinge region; and 
 folate or a folate analog, 
   
       thereby triggering ADCC, against FRA-expressing cancer cells, in neutrophils in the subject. 
     
     
         11 . The method of  claim 10 , wherein the cancer cells are breast cancer, ovarian cancer, or lung cancer cells. 
     
     
         12 . The method of  claim 10 , wherein the cancer cells are triple negative breast cancer cells. 
     
     
         13 . The method of  claim 10 , wherein the cancer cells that lack receptors for one or more of estrogen, progesterone and epithelial growth factor. 
     
     
         14 . The method of  claim 10 , wherein administration is by intravenous administration. 
     
     
         15 . The method of  claim 10 , wherein the conjugate is formulated for intravenous administration. 
     
     
         16 . The method of  claim 10 , wherein the administering comprises contacting a FRA-expressing cancer cell in the subject with the conjugate.