Agatolimod (also known as CpG 7909, ODN 2006, PF-3512676, VaxImmune, and ProMuneT) is a CpG Oligodeoxynucleotide which acts as a toll-like receptor 9agonist. Agatolimod stimulates the immune system and has been tested for prevention and treatment of cancer, infectious diseases, allergies, and asthma. [1]
The immune system is a host defense system comprising many biological structures and processes within an organism that protects against disease. To function properly, an immune system must detect a wide variety of agents, known as pathogens, from viruses to parasitic worms, and distinguish them from the organism's own healthy tissue. In many species, there are two major subsystems of the immune system: the innate immune system and the adaptive immune system. Both subsystems use humoral immunity and cell-mediated immunity to perform their functions. In humans, the blood–brain barrier, blood–cerebrospinal fluid barrier, and similar fluid–brain barriers separate the peripheral immune system from the neuroimmune system, which protects the brain.
DNA vaccination is a technique for protecting against disease by injection with genetically engineered plasmid containing the DNA sequence encoding the antigen(s) against which an immune response is sought, so cells directly produce the antigen, causing a protective immunological response. DNA vaccines have theoretical advantages over conventional vaccines, including the ability to induce a wider range of immune response types.
The CpG sites or CG sites are regions of DNA where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5' → 3' direction. CpG sites occur with high frequency in genomic regions called CpG islands. Cytosines in CpG dinucleotides can be methylated to form 5-methylcytosines. Enzymes that add a methyl group are called DNA methyltransferases. In mammals, 70% to 80% of CpG cytosines are methylated. Methylating the cytosine within a gene can change its expression, a mechanism that is part of a larger field of science studying gene regulation that is called epigenetics.
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies, while immunotherapies that reduce or suppress are classified as suppression immunotherapies.
CD32, also known as FcγRII or FCGR2, is a surface receptor glycoprotein belonging to the Ig gene superfamily. CD32 can be found on the surface of a variety of immune cells. CD32 has a low-affinity for the Fc region of IgG antibodies in monomeric form, but high affinity for IgG immune complexes. CD32 has two major functions: cellular response regulation, and the uptake of immune complexes. Cellular responses regulated by CD32 include phagocytosis, cytokine stimulation, and endocytic transport. Dysregulated CD32 is associated with different forms of autoimmunity, including systemic lupus erythematosus. In humans, there are three major CD32 subtypes: CD32A, CD32B, and CD32C. While CD32A and CD32C are involved in activating cellular responses, CD32B is inhibitory.
Pseudomonas fluorescens is a common Gram-negative, rod-shaped bacterium. It belongs to the Pseudomonas genus; 16S rRNA analysis has placed P. fluorescens in the P. fluorescens group within the genus, to which it lends its name.
Heparin-induced thrombocytopenia (HIT) is the development of thrombocytopenia, due to the administration of various forms of heparin, an anticoagulant. HIT predisposes to thrombosis because platelets release microparticles that activate thrombin, thereby leading to thrombosis. When thrombosis is identified the condition is called heparin-induced thrombocytopenia and thrombosis (HITT). HIT is caused by the formation of abnormal antibodies that activate platelets. If someone receiving heparin develops new or worsening thrombosis, or if the platelet count falls, HIT can be confirmed with specific blood tests.
Nickelocene is the organonickel compound with the formula Ni(η5-C5H5)2. Also known as bis(cyclopentadienyl)nickel or NiCp2, this bright green paramagnetic solid is of enduring academic interest, although it does not yet have any known practical applications.
Chemokine ligands 4, also known as CCL4, is a protein which in humans is encoded by the CCL4 gene.
Tremelimumab is a fully human monoclonal antibody against CTLA-4. It is an immune checkpoint blocker. Previously in development by Pfizer, it is now in investigation by MedImmune, a wholly owned subsidiary of AstraZeneca. It has been undergoing human trials for the treatment of various cancers but has not attained approval for any.
A malaria vaccine is a vaccine that is used to prevent malaria. The only approved vaccine as of 2015 is RTS,S, known by the trade name Mosquirix. It requires four injections, and has a relatively low efficacy. Due to this low efficacy, the World Health Organization (WHO) does not recommend the routine use of the RTS,S vaccine in babies between 6 and 12 weeks of age.
The Gomphales are an order of basidiomycete fungi. Some or all families belonging to Gomphales have been sometimes included in the order Phallales, the now-obsolete Ramariaceae was also previously included in Cantharellales. Recent phylogenetic analyses include in Gomphales the families of the original description of the order by Walter Jülich, with addition of Clavariadelphaceae. According to one 2008 estimate, the Gomphales contain 18 genera and 336 species.
Toll-like receptor 9 is a protein that in humans is encoded by the TLR9 gene. TLR9 has also been designated as CD289. It is a member of the toll-like receptor (TLR) family. TLR9 is an important receptor expressed in immune system cells including dendritic cells, macrophages, natural killer cells, and other antigen presenting cells. TLR9 preferentially binds DNA present in bacteria and viruses, and triggers signaling cascades that lead to a pro-inflammatory cytokine response. Cancer, infection, and tissue damage can all modulate TLR9 expression and activation. TLR9 is also an important factor in autoimmune diseases, and there is active research into synthetic TLR9 agonists and antagonists that help regulate autoimmune inflammation.
C-type lectin domain family 4 member M is a protein that in humans is encoded by the CLEC4M gene. CLEC4M has also been designated as CD299.
CpG oligodeoxynucleotides are short single-stranded synthetic DNA molecules that contain a cytosine triphosphate deoxynucleotide ("C") followed by a guanine triphosphate deoxynucleotide ("G"). The "p" refers to the phosphodiester link between consecutive nucleotides, although some ODN have a modified phosphorothioate (PS) backbone instead. When these CpG motifs are unmethylated, they act as immunostimulants. CpG motifs are considered pathogen-associated molecular patterns (PAMPs) due to their abundance in microbial genomes but their rarity in vertebrate genomes. The CpG PAMP is recognized by the pattern recognition receptor (PRR) Toll-Like Receptor 9 (TLR9), which is constitutively expressed only in B cells and plasmacytoid dendritic cells (pDCs) in humans and other higher primates.
Immunotransplant is a maneuver used to make vaccines more powerful. It refers to the process of infusing vaccine-primed T lymphocytes into lymphodepleted recipients for the purpose of enhancing the proliferation and function of those T cells and increasing immune protection induced by that vaccine.
PfSPZ Vaccine is a candidate malaria vaccine made of non-replicating irradiated whole sporozoites and developed by Sanaria. PfSPZ is the acronym of words: Plasmodium falciparum (Pf) and sporozoites (SPZ). Clinical trials have been promising, but it has been subject to some criticism regarding its ultimate feasibility with regard to large-scale production and delivery in Africa, since it must be stored in liquid nitrogen.
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a family of proteins present on the membrane surface of red blood cells that are infected by the malarial parasite Plasmodium falciparum. PfEMP1 is synthesized during the parasite's blood stage inside the RBC, during which the clinical symptoms of falciparum malaria are manifested. Acting as both an antigen and adhesion protein, it is thought to play a key role in the high level of virulence associated with P. falciparum. It was discovered in 1984 when it was reported that infected RBCs had unusually large-sized cell membrane proteins, and these proteins had antibody-binding (antigenic) properties. An elusive protein, its chemical structure and molecular properties were revealed only after a decade, in 1995. It is now established that there is not one but a large family of PfEMP1 proteins, genetically regulated (encoded) by a group of about 60 genes called var. Each P. falciparum is able to switch on and off specific var genes to produce a functionally different protein, thereby evading the host's immune system. RBCs carrying PfEMP1 on their surface stick to endothelial cells, which facilitates further binding with uninfected RBCs, ultimately helping the parasite to both spread to other RBCs as well as bringing about the fatal symptoms of P. falciparum malaria.
Dagrocorat is a nonsteroidal but steroid-like selective glucocorticoid receptor modulator (SGRM) which was under development for the treatment of rheumatoid arthritis but was never marketed. It is described as a partial agonist and "dissociable" agonist of the glucocorticoid receptor. The drug reached phase I clinical trials prior to the discontinuation of its development. The C2α dihydrogen phosphate ester of dagrocorat, fosdagrocorat, was also under investigation, but its development was terminated as well.
Fosdagrocorat is a nonsteroidal but steroid-like selective glucocorticoid receptor modulator (SGRM) which was under development for the treatment of rheumatoid arthritis but was never marketed. It is the C2 dihydrogen phosphate ester of dagrocorat, and acts as a prodrug of dagrocorat with improved pharmacokinetics. The drug reached phase II clinical trials prior to the discontinuation of its development.
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