Conformational epitope vaccines and applications
A technology of conformational epitope and vaccine composition, which is applied in the direction of chemical instruments and methods, medical preparations containing active ingredients, antibody medical ingredients, etc., can solve the problem of insufficient immunogenicity, further improvement of anti-tumor effect, failure to Stimulate an immune response, etc.
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Embodiment 1
[0146] Tumor vaccine development targeting human MUC1
[0147] Mucin 1 (MUC1) is a large single-peptide chain transmembrane glycoprotein that is autocatalytically cleaved into two subunits inside the cell and forms a heterodimer outside the cell. MUC1 contains a large extracellular domain (VNTR) consisting of 20 amino acid peptide chain repeats and is highly glycosylated. Normally, MUC1 is expressed on secretory epithelial cells and forms a protective layer. However, in a variety of tumors, such as breast cancer, pancreatic cancer, and lung cancer, MUC1 shows significant high expression, incomplete glycosylation, and severe poor prognosis. Multiple studies have shown that MUC1 promotes the loss of polarity of epidermal cells, activates multiple signal transduction pathways related to cell survival and growth, such as tyrosine kinase receptor signal transduction pathways, and resistance to cell death pathways to promote the development of tumor cells. growth and invasion. Th...
Embodiment 2
[0175] Tumor vaccine development targeting murine MUC1
[0176] Step 1 Design of Epitope Insertion Vaccine
[0177] Referring to general method 1, five different epitope prediction methods based on protein amino acid ratio and 3D structure were used to predict B cell epitopes of CTB, and 5 epitopes were successfully predicted. Among them, the best B epitope is located on V 50 –A 70 and A 70 –N 103 area, V 52 –A 59A ring-shaped region located on the outer surface of the CTB pentamer and is the common coverage area of the results of the five prediction methods. In addition, E 51 –S 55 is thought to be involved in the formation of pentamers, therefore, Q 56 –D 59 Possibly the most immunogenic epitope capable of presenting MUCl peptide.
[0178] In this embodiment, the Q56-D59 amino acids of CTB are replaced with 20 amino acids of the mouse MUC1 peptide VNTR fragment (NH 2 - DSTSSPVAHSGTSSPATSAP -COOH, SEQ ID NO.:4), designed epitope vaccine CTB-mMUC1. The amino a...
Embodiment 3
[0193] Development of tumor vaccines targeting murine MUC1 and murine PD-1
[0194] Programmed death receptor 1 (PD-1), a member of the B7-CD28 family, is an immunosuppressive receptor expressed on activated CD4+\CD8+T cells, monocytes, NK cells, and B cells. Binding of PD-1 to its ligand PDL-1 / 2 expressed on APCs inhibits T cell receptor signaling and downregulates the expression of anti-apoptotic factors (Bcl-xl) and pro-inflammatory factors. High expression of PD-1 on tumor-infiltrating lymphocytes is associated with damage to effector cells (cytokine production and cytokine antitumor effects) and poor prognosis in a variety of tumors. Therefore, blocking the tumor immunosuppression mediated by PD-1 and its ligands will be a very effective way to strengthen the tumor immune response and enhance the efficacy of anti-tumor drugs. Recent studies have shown that the use of monoclonal antibodies to double block the signal transduction pathways mediated by PD-1 and CTLA-4 combin...
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