US2002040062A1PendingUtilityA1

Protein kinase C activators and their use in decreasing expression of cell antigens

49
Assignee: UNIV COLUMBIAPriority: Sep 21, 1993Filed: Feb 13, 2001Published: Apr 4, 2002
Est. expirySep 21, 2013(expired)· nominal 20-yr term from priority
Inventors:Paul FisherJorge A. Leon
A61P 35/00A61K 31/165C07C 233/43A61K 31/23
49
PatentIndex Score
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Claims

Abstract

A composition for the upregulation of expression of cell antigens, without inducing shedding, which comprises a protein kinase C activator is provided for this invention. Further provided by this invention is a method of detecting and treating tumor cells comprising contacting tumor cells with an effective amount of a protein kinase C activator for the upregulation of expression of antigens of tumor cells, without inducing antigen shedding, and detecting the presence of said antigen or then further contacting said tumor cells with an effective amount of an antibody directed to said antigen.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A composition for the upregulation of expression of cell antigens without inducing shedding which comprises a protein kinase C activator for the upregulation of expression of a cell antigen without inducing shedding of said antigen from the cell.  
     
     
         2 . The composition of  claim 1 , wherein the protein kinase C activator is a synthetic protein kinase C activator.  
     
     
         3 . The composition of  claim 2 , wherein the protein kinase C activator is 3-(N-acetylamino)-5-(N-decyl-N-methylamino)-benzyl alcohol.  
     
     
         4 . The composition of  claim 1 , wherein the cell antigen is a tumor associated antigen.  
     
     
         5 . The composition of  claim 1 , wherein the cell antigen is a cell surface antigen.  
     
     
         6 . The composition of  claim 4 , wherein the cell antigen is a histocompatibility antigen.  
     
     
         7 . The composition of  claim 4 , wherein the tumor of the tumor associated antigen is a breast carcinoma.  
     
     
         8 . The composition of  claim 4 , wherein the tumor of the tumor associated antigen is a colon carcinoma.  
     
     
         9 . The composition of  claim 7 , wherein the tumor associated antigen is BCA 225.  
     
     
         10 . The composition of  claim 7 , wherein the tumor associated antigen is c-erb B2.  
     
     
         11 . The composition of  claim 7 , wherein the tumor associated antigen is carcinoembryonic antigen.  
     
     
         12 . The composition of  claim 7 , wherein the cell surface antigen is intercellular adhesion molecule-1.  
     
     
         13 . The composition of  claim 7  or  8 , wherein the antigen is a histocompatibility antigen.  
     
     
         14 . The composition of  claim 13 , wherein the antigen is Class II HLA-DR.  
     
     
         15 . The composition of  claim 8 , wherein the antigen is CA19.9.  
     
     
         16 . A method for decreasing tumor cell heterogeneity by upregulating the expression of an antigen without inducing shedding of said antigen which comprises administering an amount of a protein kinase C activator to cells to induce upregulation of expression of an antigen without inducing shedding of said antigen.  
     
     
         17 . The method of  claim 16 , wherein the protein kinase C activator is a synthetic protein kinase C activator.  
     
     
         18 . The method of  claim 17 , wherein the protein kinase C activator is 3-(N-acetylamino)-5-(N-decyl-N-methylamino)-benzyl alcohol.  
     
     
         19 . The method of  claim 16 , wherein the antigen is a tumor associated antigen.  
     
     
         20 . The method of  claim 16 , wherein the antigen is a histocompatibility antigen.  
     
     
         21 . The method of  claim 16 , wherein the antigen is a cell surface antigen.  
     
     
         22 . The method of  claim 19 , wherein the tumor of the tumor associated antigen is a breast carcinoma.  
     
     
         23 . The method of  claim 19 , wherein the tumor of the tumor associated antigen is a colon carcinoma.  
     
     
         24 . The method of  claim 22 , wherein the tumor associated antigen is BCA 225.  
     
     
         25 . The method of  claim 22 , wherein the tumor associated antigen is carcinoembryonic antigen.  
     
     
         26 . The method of  claim 22 , wherein the tumor associated antigen is c-erb B2.  
     
     
         27 . The method of  claim 22 , wherein the cell surface antigen is intercellular adhesion molecule-1.  
     
     
         28 . The method of  claim 22  or  23 , wherein the antigen is a histocompatibility antigen.  
     
     
         29 . The method of  claim 28 , wherein the antigen is Class II HLA-DR.  
     
     
         30 . The method of  claim 23 , wherein the antigen is CA19.9.  
     
     
         31 . The method of  claim 18 , wherein the amount is from about 0.01 μg/ml to about 10 μg/ml.  
     
     
         32 . The method of  claim 21 , wherein the cell surface antigen is intercellular adhesion molecule-1.  
     
     
         33 . A method of detecting tumor cells comprising contacting tumor cells with an effective amount of a protein kinase C activator for the upregulation of expression of cell antigens of tumor cells, without inducing antigen shedding, and detecting the presence of said antigen.  
     
     
         34 . The method of  claim 33 , wherein the protein kinase C activator is a synthetic protein kinase C activator.  
     
     
         35 . The method of  claim 34 , wherein the protein kinase C activator is 3-(N-acetylamino)-5-(N-decyl-N-methylamino)-benzyl alcohol.  
     
     
         36 . The method of  claim 33 , wherein the cell antigen is a tumor associated antigen  
     
     
         37 . The method of  claim 33 , wherein the cell antigen is a cell surface antigen.  
     
     
         38 . The method o  claim 33 , wherein the cell antigen is a histocompatibility antigen.  
     
     
         39 . The method of  claim 36 , wherein the tumor of the tumor associated antigen is a breast carcinoma.  
     
     
         40 . The method of  claim 36 , wherein the tumor of the tumor associated antigen is a colon carcinoma.  
     
     
         41 . The method of  claim 39 , wherein the antigen is the tumor associated antigen is BCA 225.  
     
     
         42 . The method of  claim 39 , wherein the antigen is the tumor associated antigen is carcinoembryonic antigen.  
     
     
         43 . The method of  claim 39 , wherein antigen is the tumor associated antigen is c-erb B2.  
     
     
         44 . The method of  claim 39 , wherein the antigen is the cell surface antigen intercellular adhesion molecule-1.  
     
     
         45 . The method of  claim 39  or  40 , wherein the antigen is a histocompatibility antigen.  
     
     
         46 . The method of  claim 45 , wherein the antigen is Class II HLA-DR.  
     
     
         47 . The method of  claim 40 , wherein the antigen is CA19.9.  
     
     
         48 . The method of  claim 35 , wherein the effective amount is from about 0.01 μg/ml to about 10 μg/ml.  
     
     
         49 . A method of treating tumor cells comprising contacting tumor cells with an effective amount of a protein kinase C activator for the upregulation of expression of cell antigens of tumor cells without inducing antigen shedding and then contacting said tumor cells with an effective amount of an antibody directed to said antigen.  
     
     
         50 . The method of  claim 49 , wherein the protein kinase C activator is a synthetic protein kinase C activator.  
     
     
         51 . The method of  claim 50 , wherein the protein kinase C activator is 3-(N-acetylamino)-5-(N-decyl-N-methylamino)-benzyl alcohol.  
     
     
         52 . The method of  claim 51 , wherein the effective amount is from about 0.01 μg/ml to about 10 μg/ml.  
     
     
         53 . The method of  claim 49 , wherein the cell antigen is a tumor associated antigen.  
     
     
         54 . The method of  claim 49 , wherein the cell antigen is a cell surface antigen.  
     
     
         55 . The method of  claim 49 , wherein the cell antigen is a histocompatibility antigen.  
     
     
         56 . The method of  claim 53 , wherein the tumor cells are breast carcinoma cells.  
     
     
         57 . The method of  claim 53 , wherein the tumor cells are colon carcinoma cells.  
     
     
         58 . The method of  claim 52 , wherein the antigen is the tumor associated antigen BCA 225.  
     
     
         59 . The method of  claim 52 , wherein the tumor associated antigen is carcinoembryonic antigen.  
     
     
         60 . The method of  claim 52 , wherein the tumor associated antigen is c-erb B2.  
     
     
         61 . The method of  claim 52 , wherein the cell surface antigen is intercellular adhesion molecule-1.  
     
     
         62 . The method of  claim 56  or  57 , wherein the antigen is a histocompatibility antigen.  
     
     
         63 . The method of  claim 62 , wherein the antigen is Class II HLA-DR.  
     
     
         64 . The method of  claim 57 , wherein the antigen is CA19.9.  
     
     
         65 . A pharmaceutical composition for upregulating the expression of antigens without inducing antigen shedding which comprises a pharmaceutically acceptable carrier and an effective amount of a protein kinase C activator.  
     
     
         66 . The pharmaceutical composition of  claim 65 , wherein the protein kinase C activator is a synthetic protein kinase C activator.  
     
     
         67 . The pharmaceutical composition of  claim 66 , wherein the protein kinase C activator is 3-(N-acetylamino)-5-(N-decyl-N-methylamino)-benzyl alcohol.  
     
     
         68 . The pharmaceutical composition of  claim 67 , wherein the effective amount is from about 0.01 μg/ml to about 10 μg/ml.  
     
     
         69 . The composition of  claim 65 , wherein the antigen is a tumor associated antigen.  
     
     
         70 . The composition of  claim 65 , wherein the antigen is a histocompatibility antigen.  
     
     
         71 . The composition of  claim 65 , wherein the antigen is a cell surface antigen.  
     
     
         72 . The composition of  claim 69 , wherein the tumor of the tumor associated antigen is a breast carcinoma.  
     
     
         73 . The composition of  claim 63 , wherein the tumor of the tumor associated antigen is a colon carcinoma.  
     
     
         74 . The composition of  claim 72 , wherein the tumor associated antigen is BCA 225.  
     
     
         75 . The composition of  claim 72 , wherein the tumor associated antigen is carcinoembryonic antigen.  
     
     
         76 . The composition of  claim 72 , wherein the tumor associated antigen is c-erb B2.  
     
     
         77 . The composition of  claim 72 , wherein the cell surface antigen is intercellular adhesion molecule-1.  
     
     
         78 . The composition of  claim 72  or  73 , wherein the antigen is a histocompatibility antigen.  
     
     
         79 . The composition of  claim 78 , wherein the antigen is Class II HLA-DR.  
     
     
         80 . The composition of  claim 73 , wherein the antigen is CA19.9.

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