Enhancing the t-cell stimulatory capacity of human antigen presenting cells in vitro and in vivo and its use in vaccination

Abstract

We provide new methods of in vitro or in vivo enhancing the T-cell stimulatory capacity of human DCs and the use thereof in cancer vaccination. The method includes the introduction of different molecular adjuvants to human DCs by contacting or modifying them with mRNA or DNA molecule(s) encoding CD40L, and CD70 or constitutively active TLR4 (caTLR4).

What is claimed is: 
     
         1 . A method for the treatment of infectious diseases, said method comprising administering to a subject in need thereof one or more isolated mRNA molecule(s) encoding for:
 a functional immunostimulatory protein CD40L, constitutively active TLR4 (caTLR4), and a functional immunostimulatory protein CD70; wherein said method does not include the administration of dendritic cells to said subject.   
     
     
         2 . The method according to  claim 1 , additionally comprising administering target-specific antigen(s) before, after, or simultaneously with the one or more isolated mRNA molecule(s). 
     
     
         3 . The method of  claim 2 , wherein the target-specific antigen(s) is selected from a bacterial antigen, a viral antigen, or a fungal antigen. 
     
     
         4 . The method of  claim 2 , wherein said target-specific antigen(s) is selected from the group consisting of: total mRNA isolated from (a) target cell(s), one or more specific target mRNA molecules, protein lysates of (a) target cell(s), specific proteins from (a) target cell(s), a synthetic target-specific peptide or protein, and synthetic mRNA or DNA encoding a target-specific antigen or its derived peptide(s). 
     
     
         5 . The method of  claim 1 , additionally comprising the administration of mRNA or DNA encoding one or more of the following molecules: IL-12p70, EL-selectin, CCR7, or 4-1BBL. 
     
     
         6 . The method according to  claim 1 , wherein said one or more isolated mRNA molecule(s) encoding the immunostimulatory proteins are part of a single mRNA molecule. 
     
     
         7 . The method according to  claim 6 , wherein the single mRNA molecule is capable of expressing the two or more proteins simultaneously. 
     
     
         8 . The method according to  claim 1 , wherein said one or more isolated mRNA molecule(s) is protected. 
     
     
         9 . The method according to  claim 1 , wherein the infectious disease is selected from:
 virus-caused infections selected from: Acquired Immunodeficiency Syndrome, Adenoviridae Infections, Alphavirus Infections, Arbovirus Infections, Bell Palsy, Boma Disease, Bunyaviridae Infections, Caliciviridae Infections, Chickenpox, Common Cold, Condyloma Acuminata, Coronaviridae Infections, Coxsackievirus Infections, Cytomegalovirus Infections, Dengue, DNA Virus Infections, Contagious Ecthyma, Encephalitis, Arbovirus-Encephalitis, Herpes Simplex, Epstein-Barr Virus Infections, Erythema Infectiosum, Exanthema Subitum, Fatigue Syndrome, Chronic Hantavirus Infections, Hemorrhagic Fevers, Viral Hepatitis, Viral Human Herpes, Labia Herpes, Simplex Herpes, Zoster Herpes, Zoster Oticus Herpesviridae Infections, HIV Infections, Infectious Mononucleosis, Influenza in Birds, Influenza, Human Lassa Fever, Measles, Meningitis, Viral Molluscum Contagiosum, Monkeypox, Mumps, Myelitis, Papillomavirus infections, Paramyxoviridae Infections, Phlebotomus Fever, Poliomyelitis, Polyomavirus Infections, Postpoliomyelitis Syndrome, Rabies, Respiratory Syncytial Virus infections, Rift Valley Fever, RNA Virus Infections, Rubella, Severe Acute Respiratory Syndrome, Slow Virus Diseases, Smallpox, Subacute Sclerosing Panencephalitis, Tick-Borne Diseases, Tumor Virus Infections, Warts, West Nile Fever, Yellow Fever, or Zoonoses; or   bacteria- or fungus-caused infections selected from: Abscess, Actinomycosis, Anaplasmosis, Anthrax, Arthritis, Reactive Aspergillosis, Bacteremia, Bacterial Infections, Mycoses,  Bartonella  Infections, Botulism, Brain Abscess, Brucellosis,  Burkholderia  Infections,  Campylobacter  Infections, Candidiasis Vulvovaginal, Cat-Scratch Disease, Cellulitis, Central Nervous System Infections, Chancroid,  Chlamydia  Infections, Chlamydiaceae Infections, Cholera,  Clostridium  Infections, Coccidioidomycosis, Corneal Ulcer-Cross Infection, Cryptococcosis, Dermatomycoses, Diphtheria, Ehrlichiosis, Empyema, Pleural Endocarditis, Bacterial Endophthalmitis, Enterocolitis, Pseudomembranous Erysipelas,  Escherichia coli  Infections, Fasciitis, Necrotizing Fournier Gangrene, Furunculosis,  Fusobacterium  Infections, Gas Gangrene, Gonorrhea, Gram-Negative Bacterial Infections, Gram-Positive Bacterial Infections, Granuloma Inguinale, Hidradenitis Suppurativa, Histoplasmosis, Hordeolum, Impetigo,  Klebsiella  Infections, Legionellosis, Leprosy, Leptospirosis,  Listeria  Infections, Ludwig's Angina, Lung Abscess, Lyme Disease, Lymphogranuloma Venereum, Maduromycosis, Melioidosis, Meningitis Bacterial,  Mycobacterium  Infections,  Mycoplasma  infections, Mycoses,  Nocardia  Infections, Onychomycosis, Osteomyelitis, Paronychia, Inflammatory Disease, Plague, Pneumococcal Infections,  Pseudomonas  Infections, Psittacosis, Puerperal Infection, Q Fever, Rat-Bite Fever, Relapsing Fever, Respiratory Tract Infections, Retropharyngeal Abscess, Rheumatic Fever, Rhinoscleroma,  Rickettsia  Infections, Rocky Mountain Spotted Fever,  Salmonella  Infections, Scarlet Fever, Scrub Typhus, Sepsis, Sexually Transmitted Diseases, Bacterial Sexually Transmitted Diseases, Bacterial Shock, Septic Skin Diseases, Bacterial Skin Diseases, infectious Staphylococcal Infections, Streptococcal Infections, Syphilis, Syphilis Congenital, Tetanus, Tick-Borne Diseases, Tinea, Tinea  Versicolor , Trachoma, Tuberculosis, Spinal Tularemia, Typhoid Fever, Typhus Epidemic Louse Borne, Urinary Tract Infections, Whipple Disease, Whooping Cough,  Vibrio  Infections, Yaws,  Yersinia  Infections, Zoonoses, or Zygomycosis.   
     
     
         10 . The method according to  claim 1 , wherein the method does not include the administration of a target specific antigen to said subject.