posted 04-14-2015 02:24 AM
Peptides are abundantly used for studies in immunotherapy, vaccination, and indeed many other areas of advanced research. There are a several number of previously manufactured peptide drugs, and the prospects for the development of new peptide drugs are very encouraging. Most of these peptides are prepared by chemical synthesis, where solid-phase peptide synthesis is the predominant method for preparation of peptides on a laboratory scale and increasingly also on an industrial scale. Allergens are a type of antigen that produces an abnormally vigorous immune response in which the immune system fights off a perceived threat that would otherwise be harmless to the body. This type of reactions termed allergies. In scientific language, an allergen is an antigen able to stimulating a type-I hypersensitivity reaction in atopic individuals through Immunoglobulin E (IgE) responses. Most of the humans mount significant IgE responses only as a defense against parasitic infections. However, several individuals may respond to common environmental antigens. This hereditary predisposition is called atopy. In atopic human being, non-parasitic antigens provoke inappropriate IgE production, leading to type I hypersensitivity. One recent report over Specific allergen immunotherapy (SIT) is disease modifying and effective. However, the use of whole-allergen preparations is related with frequent allergic adverse events during treatment. Numerous novel strategies are being designed and develpoed to reduce the allergenicity of immunotherapy preparations while maintaining immunogenicity. One approach is the use of short synthetic protein peptides that represent dominant T-cell epitopes of the allergen. Short protein peptides exhibit markedly reduced ability to cross-link IgE and trigger mast cells and basophils due to a lack of tertiary structure. Rodent preclinical studies have established the prospect of this approach, and clinical studies are currently in progress in allergic and autoimmune diseases. In short, peptide immunotherapy has been shown to improve clinical outcomes and surrogate markers in a variety of studies. Short antigen peptides (less than 20 amino acids) emerge to have remarkably reduced potential to cross-link allergen-specific IgE and are less allergenic than the entire molecule. Several studies in both allergic and autoimmune diseases support the potential of this approach. However, significant issues still need to be addressed, including whether delivery of T-cell epitopes without competent B-cell epitopes will be sufficient to provide efficacy equivalent to conventional, whole-allergen immunotherapy. Several recent avenues of documents suggest that this type of reactions might be avoided with lower peptide doses, which are still capable of inducing tolerance. One peptide can contain several overlapping T-cell epitopes with affinity for a range of MHC molecules which are required with preparations of short peptides derived from the sequences of other allergens. In conclusion, Treatment of allergic reaction by short antigen peptide based immunotherapy with or without the help of natural products effectively responds. A better understanding of the regulation and function of immune cells help to established effective immunotherapy against allergy.
ROLE OF ANTIGENS IN MACROPHAGES BASED CANCER IMMUNOTHERAPY Short antigen peptides are abundantly used for immunotherapy and indeed many other areas of advanced research. There are a several number of previously manufactured peptide drugs, and the prospects for the development of new peptide based drugs are very interesting. Most of these peptides are prepared by chemical synthesis, where solid-phase peptide synthesis is the predominant method for preparation of peptides on a laboratory scale and increasingly also on an industrial scale. Macrophages are professional antigen presenting cells (APC), which present soluble tumor associated antigens (TAAs) to the lymphocytes in association with MHC class I and class II molecules . Interaction of lymphocyte with the antigens expressed on the cell surface of macrophages results in the activation of both macrophages and lymphocytes and the activation of effector arm of the immune system. Macrophages secret a vast range of modulating products, which can express cytostatic and cytotoxic activities for tumor cells. These effects are mediated by various cytokines (IFNs, TNF-a, IL-6, IL-1a/b), reactive intermediates of oxygen and nitrogen, enzymes (e.g. arginase), metabolizing essential amino acids, prostanoid metabolites (e.g. PGE2) and nucleotides (e.g. thymidine) secreted by macrophages in the tumor-microenvironment . Tumor-derived soluble factors transform normal resident macrophages i.e. classically activated macrophages to polarized type II (alternatively activated) or M2 macrophages, that have poor antigen-presentation capability, suppressed expression of effector molecule, and are generally better adapted to scavenging debris, promoting angiogenesis and repairing, remodeling wounded/damaged tissues, and promote tumor progression by releasing a vast array of effector molecules and growth factors. A better understanding of the regulation and function of TAMs may help to established effective cancer immunotherapy for cancer regression. Treatment of cancer by macrophage-based cancer immunotherapy with or without the help of Short antigen peptides effectively respond and used in vaccination. References 1. Gautam et. al. Role of Macrophage in Tumor Microenvironment: Prospect in Cancer Immunotherapy. Euro.J. Inflam. 2013;10:1-14.
ROLE OF GENE THERAPY IN TUMOR REGRESSION
The concept of transferring genes to tissues for clinical applications has been discussed for nearly half a century, but the ability to manipulate DNA sequences or genetic material via recombinant DNA technology has brought this aim to reality. The life-threatening disorders (inborn errors, cancers) refractory to conventional treatment, gene therapy now is considered for many non–life-threatening conditions, including those negatively affecting human life. The lack of appropriate treatment has become a rational basis for extending the scope of gene therapy. Despite some well-publicized problems, gene therapy has made substantive progress, including tangible success, albeit much slower than was initially predicted. Although gene therapy is still at a fairly primitive stage. In the last decade, tumor cells genetically modified with cytokines, adhesion or MHC molecule expression have been examined for their anti-tumor effects in animal studies. These genetic modifications of tumor cells allow the induction of an immune response or facilitate tumor cell recognition or tumor cell killing by activating host immune system. Tumor cells nucleofected with the GM-CSF gene have been shown to enhance the number of antigen presenting cells (macrophages and/or dendritic cells) and induce the CD4+ and CD8+ T cells. When highly metastatic PC-3M human prostate cancer cells nucleofected with the IFN-β gene were injected s.c. into the prostate of nude mice, no tumor growth and metastases were found in mice while rapidly growing tumors and regional lymph node metastases were observed in mice injected with the parental cells. IFN- β-secreting tumor cells were also able to suppress tumor growth of bystander non-transduced tumor cells. Immunohistochemical analysis revealed that IFN-β-infected PC-3M tumor cells were heavily infiltrated with macrophages in contrast to the parental tumor cells. In T and NK cell compromised animals injected with IFN-β gene nucleofected PC-3M cells, only small avascularized tumors were present in contrast to tumors of animals injected with parental PC-3M cells or cells nucleofected with a control vector. These results indicate that inhibition of vascularization and the infiltration of macrophages due to the production of IFN-β are responsible for tumor growth inhibition and metastases were found in mice while rapidly growing tumors and regional lymph node metastases were observed in mice injected with the parental cells. IFN- β-secreting tumor cells were also able to suppress tumor growth of bystander non-transduced tumor cells. References 1. Bausero MA, Panoskaltsismortari A, Blazar BR, Katsanis E. Effective immunization against neuroblastoma using doubletransduced tumor cells secreting GM-CSF interferon-gamma. J Immunother 1996; 19:113-17. 2. Soiffer R, Lynch T, Mihm M, et al. Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte- macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma. Proc Natl Acad Sci 1998; 95:131-41. 3. T. Satoh, T. Saika, S. Ebara, et al. Prolonged, NK cell-mediated antitumor effects of suicide gene therapy combined with monocyte chemoattractant Protein-1 against hepatocellular carcinoma. Cancer Res 2003; 63:7853–60. 4. Gautam et. al. Role of Macrophage in Tumor Microenvironment: Prospect in Cancer Immunotherapy. Euro.J. Inflam. 2013;10:1-14.
------------------ As a pioneer in oligonucleotide synthesis, Bio-Synthesis has been pursuing the development of new oligonucleotide-based techniques that can produce compounds with superior binding affinity and chemical/biological stability. As such, Bio-Synthesis has introduced a third generation of nucleic acid analogs, Bridged Nucleic Acid (BNA). These are RNA analogues which can be synthesized and spiked with DNA or RNA in order to modify the formation of nucleic acid helices.