Methods and compositions for promoting immunopotentiation

Abstract

This invention discloses immunopotentiating agents which stimulate an immune response. These agents are categorized into single agents that act directly, adjuvants added concurrently with the agents, or heteroconjugates. Heteroconjugate agents elicit or enhance a cellular or humoral immune response which may be specific for an epitope contained within an amino acid sequence. Enhanced hematopoieses by bone marrow stem cell recruitment was also a result of administering some of these agents. Examples of immunopotentiating agents include monoclonal antibodies and proteins derived from microorganisms (e.g., enterotoxins) which activate T cells. One method of treatment disclosed uses only the immunopotentiating agent to stimulate the immune system. Another uses adjuvants in combination with the agent. A third method employs heteroconjugates. Heteroconjugates comprise: (a) an immunopotentiating protein which is characterized as having an ability to stimulate T cells; and (b) a second protein having an amino acid sequence which includes an epitope against which a cellular or humoral response is desired. This invention also relates to a method of preparing the heteroconjugate, and to a method of stimulating the immune system in vivo in a novel way. One route of stimulation is to activate T cells, in some instances, specific subsets of T cells, by administering heteroconjugates containing an immunopotentiating protein and a second protein, to mammals. For this method of treatment, the second protein in the heteroconjugate is derived from abnormal or diseased tissue, or from an infectious agent; alternatively, the second protein is produced synthetically by standard methods of molecular biology. Sources of the second protein include tumors, viruses, bacteria, fungi, protozoal or metozoal parasites. Monoclonal antibodies or T cells prepared from mammals whose immune systems have responded to administration of the heteroconjugate may be produced and administered to induce passive immunity. A method of preparing a hybridoma which secretes said monoclonal antibodies and use of these monoclonal antibodies and T cells, are also disclosed. This invention is also directed to a vaccine comprising the heteroconjugate.

1 . An immunopotentiating composition comprising: 
 (a) an immunopotentiating protein; and    (b) a second compound having an epitope against which a cellular or humoral immune response is desired.    
   
   
       2 . The composition of  claim 1 , wherein the immunopotentiating protein comprises a protein derived from microorganisms.  
   
   
       3 . The composition of  claim 2 , wherein the protein derived from microorganisms comprises a bacterial protein.  
   
   
       4 . The composition of  claim 3 , wherein the bacterial protein comprises a staphylococcal enterotoxin.  
   
   
       5 . The composition of  claim 1 , wherein the immunopotentiating protein comprises a monoclonal antibody directed against a T cell activation molecule on the cell surface of a T cell.  
   
   
       6 . The composition of  claim 5 , wherein the T cell activation molecule comprises a variable or constant region epitope expressed on an antigen specific T cell receptor polymorphic TcR α, β, β, or δ chain.  
   
   
       7 . The composition of  claim 5 , wherein the monoclonal antibody is directed against non-polymorphic TcR-associated CD3 chains, γ, δ, or ζ.  
   
   
       8 . The composition of  claim 7 , wherein the monoclonal antibody comprises OKT3, SP34, or 64.1.  
   
   
       9 . The composition of  claim 5 , wherein the monoclonal antibody is directed against T cell surface antigens distinct from, and not physically associated on the cell surface with, TcR.  
   
   
       10 . The composition of  claim 9 , wherein the monoclonal antibody is directed against Thy-1.  
   
   
       11 . The composition of  claim 9 , wherein the monoclonal antibody is directed against an activation epitope expressed on a member of the Ly-6 protein family.  
   
   
       12 . The composition of  claim 9 , wherein the monoclonal antibody(s) is directed against human CD2.  
   
   
       13 . The composition of  claim 9 , wherein the monoclonal antibody is directed against CD28.  
   
   
       14 . The composition of  claim 1 , wherein the immunopotentiating protein is a bispecific agent, wherein one arm is specific for a T cell activation epitope, and the other arm specific for a T cell subset specific epitope.  
   
   
       15 . The composition of  claim 14 , wherein the bispecific agent comprises a union of two monoclonal antibodies one directed individually against CD3, the other against CD4.  
   
   
       16 . The composition of  claim 1 , wherein the second protein comprises a peptide of from about 8 to about 100 amino acids in length.  
   
   
       17 . The composition of  claim 1 , wherein the second protein comprises a peptide of from about 8 to about 50 amino acids in length.  
   
   
       18 . The composition of  claim 1 , wherein the second protein comprises a peptide derived from a tumor-specific or tumor-associated epitope.  
   
   
       19 . The composition of  claim 1 , wherein the second protein comprises a peptide derived from a viral-specific or viral-associated epitope.  
   
   
       20 . The composition of  claim 1 , wherein the second protein comprises a peptide with an amino acid sequence homologous to that derived from a gene in a bacteria, fungus, protozoal or metazoal parasite.  
   
   
       21 .- 54 . (canceled)