Composition and methods for affecting metallocorrinoid uptake

Abstract

The present invention is directed to compositions and methods for affecting metallocorrinoid uptake. The compositions and methods of the present invention are particularly useful in enhancing the uptake or availability of biologically active metallocorrinoids (e.g. cobalamin and its analogs). The present invention is particularly useful in the treatment or prevention of conditions that result from low expression or activity of proteins involved in the processing of metallocorrinoids, as well as in conditions which would benefit from enhanced uptake or availability of cobalamin or its biologically active analogs of cobalamin (e.g. cobalamin drug conjugates).

1 . A therapeutic composition comprising a metallocorrinoid and a cytokine.  
   
   
       2 . The therapeutic composition of  claim 1 , wherein said metallocorrinoid is vitamin B 12 .  
   
   
       3 . The therapeutic composition of  claim 1 , wherein said metallocorrinoid is a vitamin B 12  analog.  
   
   
       4 . The composition of  claim 1 , wherein said cytokine is interferon-β.  
   
   
       5 . The composition of  claim 3 , wherein said vitamin B 12  analog is nitrosylcobolamin.  
   
   
       6 . The therapeutic composition of  claim 3 , wherein said vitamin B 12  analog is selected from the group consisting of hydroxocobalamin, cyanocobalamin, methylcobalamin, 5′ deoxyadenocobalamin.  
   
   
       7 . The therapeutic composition of  claim 1  wherein said metallocorrinoid is a cobalamin drug conjugate and said cytokine is interferon-β.  
   
   
       8 . The therapeutic composition of  claim 7 , further including a pharmaceutical carrier.  
   
   
       9 . A method of enhancing uptake of a metallocorrinoid comprised of administering a cytokine.  
   
   
       10 . The method of  claim 9 , wherein said metallocorrinoid is vitamin B 12 .  
   
   
       11 . The method of  claim 9 , wherein said metallocorrinoid is a vitamin B 12  analog.  
   
   
       12 . The method of  claim 9 , wherein said cytokine is an interferon.  
   
   
       13 . The method of  claim 12 , wherein said interferon is interferon-β.  
   
   
       14 . A method of treating a patient comprising the steps of inducing cytokine production and administering a metallocorrinoid.  
   
   
       15 . The method of  claim 14 , where the step of inducing cytokine production comprises administering a cytokine.  
   
   
       16 . The method of  claim 14 , wherein said metallocorrinoid is vitamin B 12 .  
   
   
       17 . The method of  claim 14  wherein said metallocorrinoid is a vitamin B 12  analog.  
   
   
       18 . The method of  claim 14 , wherein the cytokine is interferon-β.  
   
   
       19 . A method for increasing TCII-R activity in a subject to treat a condition favorably affected by an increase in said TCII-R activity comprising the step of administering to a subject in need of such treatment a cytokine in an amount effective to increase TCII-R activity in the subject.  
   
   
       20 . The method of  claim 19 , further comprising the step of co-administering a vitamin B 12  analog.  
   
   
       21 . The method of  claim 19 , wherein said cytokine is administered prior to the vitamin B 12  analog.  
   
   
       22 . The method of  claim 19 , wherein said cytokine is administered prophylactically.  
   
   
       23 . The method of  claim 19 , wherein said cytokine is administered acutely.  
   
   
       24 . The method of  claim 19 , wherein said cytokine is an interferon.  
   
   
       25 . The method of  claim 24 , wherein said interferon is interferon-β.  
   
   
       26 . The method of  claim 19 , wherein said condition is unwanted cellular proliferation.  
   
   
       27 . A method of enhancing bio-availability of a metallocorrinoid comprising the step of administering interferon-β.  
   
   
       28 . A method of treating a subject to increase TCII-R activity in a cell comprising the step of administering to a subject in need of such treatment a cytokine in an amount effective to increase TCII-R activity in said cell.  
   
   
       29 . The method of  claim 28 , wherein the subject is cobalamin deficient.  
   
   
       30 . The method of  claim 28 , wherein the amount is sufficient to increase TCII-R activity above normal baseline levels.  
   
   
       31 . The method of  claim 28 , wherein the subject has an abnormally low level of TCII-R activity.  
   
   
       32 . The method of  claim 28 , further comprising the step of co-administering a ligand of TCII-R.  
   
   
       33 . The method of  claim 32  herein the ligand of TCII-R is cobalamin.  
   
   
       34 . The method of  claim 32 , wherein the ligand of TCII-R is a cobalamin drug conjugate.  
   
   
       35 . The method of  claim 34 , wherein the cobalamin drug conjugate is nitrosylcobalamin.