Immunoregulation in cancer, chronic inflammatory and autoimmune diseases

Abstract

The present invention primarily relates to a method for analyzing the amount of immunoregulatory integrin binding factors and/or patient endogenous antibodies which are directed against such factors, the factors having the capacity to modulate the immune functions in a subject suffering from cancer or inflammatory or autoimmune diseases, by utilizing binding reagents to determine these factors and/or the patient endogenous antibodies which are directed against such factors, whereby the prognosis and/or the therapeutic efficacy of any treatment of a subject suffering from cancer or inflammatory or autoimmune diseases can be determined and/or monitored. The invention further relates to the use of therapeutically active compounds for eliminating, inhibiting or enhancing such binding factors for the manufacture of pharmaceuticals to be used in the treatment of cancer, inflammatory conditions or autoimmune diseases.

1 . Method for analyzing the amount of integrin binding factors and/or patient endogenous antibodies directed against such factors, present and produced in tissues of cancer patients or tissues of patients with chronic inflammatory or autoimmune diseases, said factors having the capacity to modulate the immune functions in a subject suffering from cancer or inflammatory or autoimmune diseases, whereby the prognosis and/or the therapeutic efficacy of any treatment of a subject suffering from cancer or inflammatory or autoimmune diseases can be determined and/or monitored, said factors and/or the patient endogenous antibodies directed against such factors being determined by utilizing an analysis method to determine these factors and/or the patient endogenous antibodies directed against such factors.  
   
   
       2 . The method according to  claim 1 , wherein the analytical methods used include analysis using binding reagents in liquid or solid phase, electrophoretic analysis, chromatographic analysis or masspectrometric analysis.  
   
   
       3 . The method according to  claim 1 , wherein the integrin binding factors are β2-integrin or a4β1 integrin binding or blocking factors.  
   
   
       4 . The method according to  claim 1 , wherein the integrin binding factor is an integrin binding factor alone or in complex with Fc-receptor binding or blocking factors of immunoglobulins.  
   
   
       5 . The method according to  claim 1 , wherein binding reagents used for the determination of the integrin binding factors are externally produced antibodies, monoclonal antibodies and/or fragments thereof, or any synthetic constructs or reagents directed to these said factors, which reagents are present in liquid or solid phase.  
   
   
       6 . The method according to  claim 1 , wherein masspectrometry analysis includes SELDI-TOF or MALDI-TOF analysis.  
   
   
       7 . The method according to  claim 5 , wherein binding reagents used for the determination of patient endogenous antibodies directed against integrin binding factors, are selected from the group of binding reagents; binding to the epitope and/or antigenic site of integrin factors, externally produced antibodies, monoclonal antibodies and/or fragments thereof, and any synthetic constructs or reagents directed to these tissue related antibodies.  
   
   
       8 . The method according to  claim 1 , wherein cell surface substances, including integrins, are biotinylated, dissolved in the presence of a protease inhibitor and placed on a streptavidin coated surface, whereupon a determination of the binding of an antibody directed against a specific cell surface substance in the presence of a binding or blocking factor is made, whereby the amount of antibodies bound is an inverse measure of the amount blocking and/or binding factors present.  
   
   
       9 . The method according to  claim 1 , wherein cell surface binding factors present in a tissue sample of a patient after adsorption to said coated surface are determined.  
   
   
       10 . The method according to  claim 1 , wherein the amount of such integrin binding factors and/or patient endogenous antibodies directed against such factors, is used to determine the prognosis of a subject suffering from cancer.  
   
   
       11 . The method according to  claim 1 , wherein the amount of such integrin binding factors and/or patient endogenous antibodies directed against such factors, is used to determine the therapeutic efficacy of any cancer treatment.  
   
   
       12 . The method according to  claim 1 , wherein the amount of such integrin binding factors and/or patient endogenous antibodies directed against such factors, is used to determine the prognosis of a subject suffering from chronic inflammatory or autoimmune diseases.  
   
   
       13 . The method according to  claim 1 , wherein the amount of such integrin binding factors and/or patient endogenous antibodies directed against such factors, is used to determine the therapeutic efficacy of any treatment of chronic inflammatory or autoimmune diseases.  
   
   
       14 . A method for preventing, inhibiting and/or enhancing the activity of integrin binding factors which are involved in the dysregulation of immune functions, comprising administering an effective amount of monoclonal antibodies characterized by their reactivity with dHSA.  
   
   
       15 . The method according to  claim 14 , wherein the therapeutically active substances comprise compounds directed against β2-integrin or a4β1 integrin binding or blocking factors.  
   
   
       16 . The method according to  claim 14 , wherein the therapeutically active substances comprise compounds directed against integrin binding factor alone or in complex with Fc-receptor binding or blocking factors.  
   
   
       17 . The method according to  claim 15 , wherein the therapeutically active substances comprise β2-integrin binding or blocking factors, including fragments thereof.  
   
   
       18 . The method according to  claim 18 , wherein the therapeutically active substances comprise integrin binding factor alone or in complex with Fc-receptor binding or blocking factors.  
   
   
       19 . Method of therapeutic treatment by administering therapeutically active substances preventing, inhibiting and/or enhancing the activity of integrin binding factors and/or patient endogenous antibodies directed against such factors, involved in the dysregulation of immune functions, to a subject suffering from a cancer where said immune functions are suppressed, whereby the amount of such integrin binding factors are therapeutically controlled to minimize pathological production or biological activity of such integrin binding factors being immunosuppressive, to enhance the therapeutic control of a malignant tumour in a subject suffering from a cancer, or to a subject suffering from chronic inflammatory or autoimmune diseases where said immune function is over-reactive/enhanced, whereby such therapeutically active substances preventing, inhibiting and/or enhancing the activity of integrin binding factors and/or patient endogenous antibodies are therapeutically administered to enhance the performance status of the patient and/or or to achieve therapeutic control in a subject suffering from inflammatory or autoimmune diseases.