Therapeutic vaccines against cancer

The first trials of therapeutic vaccination against cancer using lipid A as adjuvant were performed on melanoma patients with 0.25 ml Detox. The composition of commercial vaccines used as therapeutic vaccines in humans is given in Table 2. Some trials used a pretreatment with 300... 

The application of the DNA vaccine technology is not limited to infectious diseases and is currently being used in therapeutic vaccines against cancer. Table 18.4 presents the therapeutic DNA vaccines under development (Powell, 2004). 

Trials of therapeutic vaccination against prostate cancer used OncoVax-P (Jenner Biotherapies, Inc, San Ramon, California). OncoVax-P consists of 200 pg monophosphoryl lipid A (similar to that used in Detox) added to 1 ml liposomes and 100 pg PSA (prostate-specific antigen). Patients received injections by different routes (intramuscular, intravenous or subcutaneous) according to the trial, with or without GM-CSF, IL-2 or BCG and cyclophosphamide pretreatment. No serious side effects were seen. DTH and antibody responses were achieved. Vaccination increased the PSA-reactive T cell frequency as determined by IFN-y secretion, but no toxicity against PSA-expressing target cells was detected. The most effective strategy could not be determined, and no conclusion about the clinical efficacy of the treatment was possible [214,215],... 

Bonnet, M. C., Tartaglia, J., Verdier, R, Kourilsky, P, Lindberg, A., Klein, M., and Moingeon, P. 2001. Recombinant viruses as a tool for therapeutic vaccination against human cancers. Immunol. Letters 74 11-25. 

Here, we present methods of preparation of liposomal vaccines and results obtained in our laboratories with small unilamellar liposomes as carriers of antigen peptides and peptide encoding DNA plasmids, demonstrating their high potential as therapeutic vaccine formulations against infectious diseases and cancers. 

Besides the attention that has been given to the development of therapeutic vaccines in the fight against cancer, therapeutic vaccines are also in development against the use of addictive drugs such as nicotine or for the treatment of autoimmune diseases [6]. 

The goal of therapeutic vaccination is to harness the power of the immune system to treat complex diseases such as cancer, autoimmunity, obesity, and Alzheimer s disease. The basic principle in the design of a therapeutic vaccine is to identify the self-protein that causes a disease, and then try to elicit an immune response against the protein, by breaking immune tolerance, in order to remove the protein from the body and alleviate the symptoms of the disease. Once immune tolerance is broken, it leads to the destruction of the targeted self-protein thus, the balance between safety and efficacy for therapeutic vaccines needs to be carefully assessed. 

Preclinical Results and Clinical Applications. Both pDNA- and mRNA-based vaccinations were demonstrated to be efflcacious in animal models as prophylactic or therapeutic immunotherapies against tumors, infectious diseases, and allergy. Two pDNA-based vaccines are commercialized for veterinary use an anti-equine fever and an anti-infectious hematopoietic necrosis virus (IHNV) for farm-raised salmons. In humans, several formulations of nucleic acid vaccines are tested in clinical trials (see the actualized list of trials at www.clinicaltrials.gov). Although pDNA-based vaccine trials were reported in the context of antitumor, antivirus (HIV, influenza virus, HBV) and antiparasite Plasmodium falciparum) approaches, mRNA-based vaccines were up to now tested only as immunotherapies against cancer (review by Liu and Ulmer for pDNA [35] and Pascolo for mRNA [36]). 

Liu, T.-Y, Hussein, W.M., Jia, Z., et al. Self-adjuvanting polymer-peptide conjugates as therapeutic vaccine candidates against cervical cancer. Biomacromolecules 14, 2798-2806 (2013). doi 10.1021/bm400626w... 

The most widely studied therapeutic proteins produced in plants include monoclonal antibodies for passive immunotherapy and antigens for use as oral vaccines [40]. Antibodies against dental caries, rheumatoid arthritis, cholera, E. coli diarrhea, malaria, certain cancers, Norwalk virus, HIV, rhinovirus, influenza, hepatitis B virus and herpes simplex virus have been produced in transgenic plants. However, the anti-Streptococcus mutans secretory antibody for the prevention of dental caries is the only plant-derived antibody currently in Phase II clinical trials [40]. Until recently, most antibodies were expressed in tobacco, potato, alfalfa, soybean, rice and wheat [9], It has been estimated that for every 170 tons of harvested tobacco, 100 tons represents harvested leaves. A single hectare could thus yield 50 kg of secretory IgA [3, 41]. Furthermore, it has been estimated that the cost of antibody production in plants is half that in transgenic animals and 20 times lower than in mammalian cell cul-... 

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