PEPTIDE VACCINE THERAPY FOR TREATMENT OF FRa-EXPRESSING TUMORS

Abstract

Provided are methods for inducing and maintaining protective immunity against a tumor expressing FRα in a subject, comprising the administration of one or more peptide vaccines according to a particular dosages or particular dosage regimens.

What is claimed is: 
     
         1 . A method of inducing an immune response against a tumor expressing folate receptor alpha (FRα) in a subject in need thereof, the method comprising:
 (a) administering a first vaccine comprising a peptide comprising the amino acid sequence of SEQ ID NO:1 (E39) and an adjuvant every three to four weeks for a period of about two to about six months; and 
 (b) subsequently administering a second vaccine comprising a peptide comprising the amino acid sequence of SEQ ID NO: 2 (E39′) and an adjuvant every three to four weeks for a period of about two to six months. 
 
     
     
         2 . The method of  claim 1 , wherein the first vaccine is administered by injection. 
     
     
         3 . The method of  claim 1 , wherein the second vaccine is administered by injection. 
     
     
         4 . The method of  claim 1 , wherein the first vaccine comprises about 0.1 mg to about 2 mg of the peptide. 
     
     
         5 . The method of  claim 4 , wherein the first vaccine comprises about 0.5 or about 1.0 mg of the peptide. 
     
     
         6 . The method of  claim 1 , wherein the second vaccine comprises about 0.1 mg to about 2 mg of the peptide. 
     
     
         7 . The method of  claim 6 , wherein the second vaccine comprises about 0.5 or about 1.0 mg of the peptide. 
     
     
         8 . The method of  claim 1 , wherein the adjuvant in the first vaccine is granulocyte macrophage-colony stimulating factor (GM-CSF). 
     
     
         9 . The method of  claim 1 , wherein the adjuvant in the second vaccine is GM-CSF. 
     
     
         10 . The method of  claim 8 , wherein the first vaccine comprises between about 0.01 to about 0.5 mg GM-CSF. 
     
     
         11 . The method of  claim 9 , wherein the second vaccine comprises between about 0.01 to about 0.5 mg GM-CSF. 
     
     
         12 . The method of  claim 1 , further comprising administering to the subject a booster composition after the primary immunization schedule is completed, wherein the booster composition comprises an effective amount of a peptide comprising an amino acid selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 2, and an adjuvant. 
     
     
         13 . The method of  claim 12 , wherein the adjuvant in the booster composition is GM-CSF in an amount between about 0.01 to about 0.5 mg. 
     
     
         14 . The method of  claim 12 , wherein the booster composition is administered about six months, about twelve months or about one year after completion of the primary immunization schedule. 
     
     
         15 . The method of  claim 1 , wherein the FRα-expressing cancer is an epithelial-derived malignancy. 
     
     
         16 . The method of  claim 15 , wherein the FRα-expressing cancer is ovarian cancer, endometrial cancer, breast cancer, cervical cancer, colorectal cancer, lung cancer, uterine cancer, osteosarcoma, renal cell carcinoma, mesothelioma, CNS sarcoma, ependyoma and pituitary adenoma. 
     
     
         17 . A method of inducing and maintaining an immune response to a tumor expressing FRα in a subject, the method comprising,
 (a) administering a first vaccine comprising between about 0.1 and about 2 mg of a peptide consisting of the amino acid sequence of SEQ ID NO:1 (E39) and an adjuvant every three to four weeks for a period of about two to about six months; 
 (b) subsequently administering a second vaccine comprising between about 0.1 and about 2 mg of a peptide consisting of the amino acid sequence of SEQ ID NO: 2 (E39′) and an adjuvant every three to four weeks for a period of about two to six months; and 
 (c) administering a booster composition comprising between about 0.1 and about 2 mg of a peptide consisting of an amino acid selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 2, and an adjuvant about six months after step (b). 
 
     
     
         18 . The method of  claim 17 , wherein the first vaccine comprises about 0.5 mg or about 1.0 mg of the peptide. 
     
     
         19 . The method of  claim 17 , wherein the booster composition comprises about 0.5 or about 1.0 mg of a peptide consisting of the amino acid sequence of SEQ ID NO: 2. 
     
     
         20 . The method of  claim 17 , wherein the adjuvant in the first vaccine, second vaccine and booster composition is GM-CSF.