Detection and treatment of infections with immunoconjugates

Abstract

A method of targeting a diagnostic or therapeutic agent to a focus of infection comprises injecting a patient infected with a pathogen parenterally with an antibody conjugate which specifically binds to an accessible epitope of the pathogen or of a pathogen-associated antigen accreted at the focus of infection, the antibody conjugate further comprising a bound diagnostic or therapeutic agent for detecting, imaging or treating the infection. Polyspecific composite conjugates enhance the efficacy of the method, which is especially useful for treating infections that are refractory towards systemic chemotherapy.

What is claimed is:  
     
         1 . A method of targeting a diagnostic or therapeutic agent to a focus of infection, which comprises injecting a patient infected with a pathogen parenterally with an antibody conjugate which specifically binds to an accessible epitope of said pathogen or of a pathogen-associated antigen accreted at said focus of infection, said antibody conjugate further comprising a bound diagnostic or therapeutic agent for detecting, imaging or treating said infection.  
     
     
         2 . The method of  claim 1 , wherein said agent is a diagnostic agent selected from the group consisting of a radioisotope and a magnetic resonance image enhancing agent.  
     
     
         3 . The method of  claim 1 , wherein said agent is a therapeutic radioisotope or boron addend.  
     
     
         4 . The method of  claim 1 , wherein said agent is an anti-pathogenic drug or cytotoxic agent.  
     
     
         5 . The method of  claim 1 , wherein said antibody conjugate specifically binds to an accessible epitope of said pathogen or pathogen-associated antigen which is not saturated or blocked by the patient's native antibodies.  
     
     
         6 . The method of  claim 5 , wherein said antibody conjugate comprises a monoclonal antibody.  
     
     
         7 . The method of claim,  1 , wherein said antibody conjugate is a polyspecific conjugate which specifically binds to a plurality of accessible epitopes of said pathogen or antigen.  
     
     
         8 . The method of  claim 7 , wherein said polyspecific antibody conjugate is an antiserum.  
     
     
         9 . The method of  claim 8 , wherein said antiserum is affinity purified by removal of antibodies which bind to antigens associated with said pathogen circulating at a significant level in the patient's bloodstream.  
     
     
         10 . The method of  claim 8 , wherein said antiserum is affinity purified by contact with bound pathogen or pathogen-associated antigens, and subsequent recovery of antiserum enriched in antibodies that bind to said pathogen or pathogen-associated antigens.  
     
     
         11 . The method of  claim 7 , wherein said polyspecific conjugate is a mixture of monoclonal antibodies.  
     
     
         12 . The method of  claim 7 , wherein said polyspecific conjugate is a chemically linked molecule having a plurality of antigen binding sites for said plurality of epitopes.  
     
     
         13 . The method of  claim 1 , wherein said pathogen is a virus.  
     
     
         14 . The method of  claim 13 , wherein said virus is an RNA virus.  
     
     
         15 . The method of  claim 13 , wherein said virus is a DNA virus.  
     
     
         16 . The method of  claim 13 , wherein said virus is selected from the group consisting of human immunodifficency virus (HIV), herpes virus, cytomegalovirus, rabies virus, influenza virus, hepatitis B virus, Sendai virus, feline leukemia virus, Reo virus, polio virus, human serum parvo-like virus, simian virus 40, respiratory syncytial virus, mouse mammary tumor virus, Varicella-Zoster virus, Dengue virus, rubella virus, measles virus, adenovirus, human T-cell leukemia viruses, Epstein-Barr virus, murine leukiemia virus, mumps virus, vesicular stomatitis virus, Sindbis virus, lymphocytic choriomeningitis virus, wart virus and blue tongue virus.  
     
     
         17 . The method of  claim 1 , wherein said pathogen is a bacterium.  
     
     
         18 . The method of  claim 17 , wherein said bacterium is selected from the group consisting of Streptococcus agalactiae,  Legionella pneumophilia, Streptococcus pyogenes, Escherichia coli, Neisseria gonorrhosae, Neisseria meningitidis , Pneumococcus, Hemophilis influenzae-B,  Treponema pallidum , Lyme disease spirochetes,  Pseudomonas aeruginosa, Mycobacterium leprae, Brucella abortus, Mycobacterium tuberculosis  and Tetanus toxin.  
     
     
         19 . The method of  claim 1 , wherein said pathogen is a protozoan.  
     
     
         20 . The method of  claim 19 , wherein said protozoan is selected from the group consisting of  Plasmodium falciparum, Plasmodium vivax, Toxoplasma gondii, Trypanosoma rangeli, Trypanosoma cruzi, Trypanosoma rhodesiensei, Trypanosoma brucei, Schistosoma mansoni, Schistosoma japanicum, Babesia bovis, Elmeria tenella, Onchocerca volvulus, Leishmania tropica, Trichinella spiralis, Onchocerca volvulus, Theileria parva, Taenia hydatigena, Taenia ovis, Taenia saginata, Echinococcus granulosus  and  Mesocestoides corti.    
     
     
         21 . The method of  claim 1 , wherein pathogen is a helminth.  
     
     
         22 . The method of  claim 1 , wherein said pathogen is mycoplasma.  
     
     
         23 . The method of  claim 22 , wherein said mycoplasma is selected from the group consisting of  Mycoplasma arthritidis, M. hyorhinis, M. orale,. M. arginini, Acholeplasma laidlawii, M. salivarium  and  M. pneumoniae.    
     
     
         24 . The method of  claim 1 , which further comprises administering to said patient, at a time after administration of said conjugate sufficient to optimize uptake of said conjugate at the site of said infection, an amount of a second antibody that specifically binds to said conjugate sufficient to reduce the amount of said conjugate in circulation by 10-85% within 2-72 hours.  
     
     
         25 . The method of  claim 1 , wherein said agent is a therapeutic antibiotic or cytotoxic agent that causes hematopoietic toxicity as a side effect of its administration, and wherein said method further comprises administering to said patient, at a time prior to, concomitant with or subsequent to administration of said therapeutic conjugate, an amount of a cytokine sufficient to mitigate or prevent the hemtopoietic toxicity of said agent.  
     
     
         26 . An antibody conjugate for targeting a focus of infection, comprising an antibody or antibody fragment which binds to an epitope on a single species of pathogen or an antigen derived therefrom, said antibody or antibody fragment being conjugated to at least one diagnostic or therapeutic agent.  
     
     
         27 . An antibody conjugate for targeting a focus of infection, comprising an immunoreactive composite of a plurality of chemically linked antibodies or antibody fragments which bind to a plurality of epitopes on a single species of pathogen or an antigen derived therefrom, said composite being conjugated to at least one diagnostic or therapeutic agent.  
     
     
         28 . A sterile injectable preparation for targeting a focus of infection in a human patient, comprising the antibody conjugate of  claim 26 , in combination with a pharmacologically acceptable sterile injection vehicle.  
     
     
         29 . A kit for use in preparing a sterile injectable preparation for targeting a focus of infection in a human patient, comprising in suitable containers, the antibody conjugate of  claim 26  and a pharmacologically acceptable sterile injection vehicle.