Annexin a2 as immunological target

Abstract

AnnexinA2 (ANXA2), a member of the Annexin family of calcium-dependent, phospholipid binding proteins, is one of a panel of identified antigens recognized by the post-vaccination sera of patients who demonstrated prolonged disease-free survival following multiple vaccinations. AnnexinA2 is abundantly expressed in pancreatic adenocarcinomas and cell surface/membrane AnnexinA2 increases with the progression from premalignant lesions to invasive pancreatic adenocarcinomas. The cytoplasmic to cell surface translocation of AnnexinA2 expression is critical for pancreatic cancer cell invasion. In addition, phosphorylation of AnnexinA2 at Tyrosine 23 is important for its localization to the cell surface and for the invasion of pancreatic cancer cells. Finally, loss of AnnexinA2 leads to the loss of the Epithelial-Mesenchymal Transition.

1 . A vaccine for treating patients with a tumor which has been resected, comprising:
 at least one T or B cell epitope of ANXA2 protein or a nucleic acid encoding ANXA2 protein, wherein the vaccine is not a whole tumor cell vaccine.   
     
     
         2 . The vaccine of  claim 1  which comprises a nucleic acid encoding ANXA2 protein. 
     
     
         3 . The vaccine of  claim 1  which comprises ANXA2 protein. 
     
     
         4 . The vaccine of  claim 3  wherein the ANXA2 protein comprises a phosphorylated Tyr23 residue. 
     
     
         5 . The vaccine of  claim 1  wherein the vaccine comprises at least one T or B cell epitope of ANXA2 protein which comprises a phosphorylated Tyr23 residue. 
     
     
         6 . The vaccine of  claim 1  further comprising a protein or nucleic acid encoding said protein selected from the group consisting of: Calumenin isoform A precursor, Chaperonin (heat shock protein 60), enolase 1 or α, Galectin 3, Keratin 19, Lactate dehydrogenase A isoform 1, Otubain 1, Peptidylprolyl isomerase A, Prolyl 4-hydroxylase, beta subunit precursor, Pyruvate kinase, muscle isoform M2, Rho GDP dissociation inhibitor (GDI) alpha, Tubulin alpha 6, Tumor protein, and translationally-controlled 1. 
     
     
         7 . The vaccine of  claim 1  further comprising at least one T or B cell epitope of a protein or a nucleic acid encoding said epitope, wherein said protein is selected from the group consisting of: Calumenin isoform A precursor, Chaperonin (heat shock protein 60), enolase 1 or α, Galectin 3, Keratin 19, Lactate dehydrogenase A isoform 1, Otubain 1, Peptidylprolyl isomerase A, Prolyl 4-hydroxylase, beta subunit precursor, Pyruvate kinase, muscle isoform M2, Rho GDP dissociation inhibitor (GDI) alpha, Tubulin alpha 6, Tumor protein, and translationally-controlled 1. 
     
     
         8 . A method of treating a patient with a tumor to diminish risk of tumor invasion and/or metastatic progression, comprising:
 administering a vaccine of  claim 1  to the patient, whereby a T cell or B cell response to ANXA2 is induced.   
     
     
         9 . The method of  claim 8  wherein the patient has had the bulk of his tumor resected. 
     
     
         10 . The method of  claim 8  wherein the tumor is a pancreatic tumor. 
     
     
         11 . The method of  claim 8  wherein the tumor is selected from the group consisting of a melanoma, a kidney tumor, a prostate tumor, and a liver tumor. 
     
     
         12 . A method of determining long term survival in a cancer patient whose tumor expresses galectin or annexinA2 on tumor cell surface, comprising:
 detecting antibodies to galectin or annexinA2 in the serum of the patient, wherein the antibodies are a positive indicator of long term survival.   
     
     
         13 . The method of  claim 12  wherein the patient has received a vaccine comprising at least one B cell epitope of galectin or annexinA2. 
     
     
         14 . The method of  claim 12  comprising prior to the step of detecting:
 admininstering to the patient a vaccine comprising at least one B cell epitope of galectin or annexinA2. 
 
     
     
         15 . An isolated siRNA molecule useful for inhibiting invasion of a cancer, wherein one strand of the siRNA is complementary to Annexin A2 mRNA. 
     
     
         16 . A pharmaceutical composition for treating cancer patients, comprising monoclonal antibodies, said antibodies specifically binding to AnnexinA2 which is phosphorylated on Tyr23. 
     
     
         17 . The composition of  claim 16  wherein the antibodies are human, humanized, or chimeric. 
     
     
         18 . A method of treating a cancer patient with a tumor to diminish risk of tumor invasion and/or metastatic progression, comprising:
 administering monoclonal antibodies which specifically bind to AnnexinA2 which is phosphorylated on Tyr23 to the patient.   
     
     
         19 . The method of  claim 18  wherein the patient has had his tumor resected. 
     
     
         20 . The method of  claim 18  wherein the tumor is a pancreatic tumor. 
     
     
         21 . The method of  claim 18  wherein the tumor is selected from the group consisting of a melanoma, a kidney tumor, a prostate tumor, and a liver tumor. 
     
     
         22 . The method of  claim 18  wherein the patient has been previously treated with chemotherapy. 
     
     
         23 . A method of treating a cancer patient with a tumor to diminish risk of tumor invasion, and/or metastatic progression, comprising:
 administering monoclonal antibodies which specifically bind to Annexin A2 to the patient, wherein the patient has been previously treated with chemotherapy.   
     
     
         24 . A method of treating a cancer patient with a tumor to diminish risk of tumor invasion, and/or metastatic progression, comprising:
 administering to the patient an allogeneic, GM-CSF-secreting, tumor cell vaccine;   and   adopting transfusing monoclonal antibodies which specifically bind to Annexin A2.   
     
     
         25 . The method of  claim 24  wherein the patient had received a pancreaticoduodenectomy. 
     
     
         26 . The method of  claim 24  wherein the patient had received radiochemotherapy.