80 results about "Antineoplastic Vaccine" patented technology

The present invention provides compositions and methods for generating and cryopreserving dendritic cells with superior functionality in producing stronger signals to T cells, resulting in a more potent DC-based anti-tumor vaccine. The present invention includes mature, antigen loaded DCs activated by Toll-like receptor agonists that induce clinically effective immune responses, preferably when used earlier in the disease process. The DCs of the present invention produce desirable levels of cytokines and chemokines, and further have the capacity to induce apoptosis of tumor cells. The cells can be cryopreserved and thawed for later use, thereby reducing the need for repeated pheresis and elutriation processes during vaccine production. These methods can also be utilized to directly target molecules involved in carcinogenetic signaling pathways and cancer stem cells.

The immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) is expressed by a subset of murine plasmacytoid DCs (pDCs) in tumor-draining LNs, where it can potently activate Foxp3 regulatory T cells (Tregs). We now show that IDO functions as a molecular switch in tumor-draining LNs, maintaining Tregs in their normal suppressive phenotype when IDO was active, but allowing inflammation-induced conversion of Tregs to a polyfunctional T-helper phenotype similar to proinflammatory TH17 cells when IDO was blocked. In vitro, conversion of Tregs to the TH17-like phenotype was driven by antigen-activated effector T cells, and required IL-6 produced by activated pDCs. IDO regulated this conversion by dominantly suppressing production of IL-6 in pDCs, in a GCN2-kinase dependent fashion. In vivo, using a model of established B16 melanoma, the combination of an IDO-inhibitor drug plus anti-tumor vaccine caused upregulation of IL-6 in pDCs and in situ conversion of a majority of Tregs to the TH17 phenotype, with marked enhancement of CD8+ T cell activation and anti-tumor efficacy. Thus, Tregs in tumor-draining LNs can be actively re-programmed in vitro and in vivo into T-helper cells, without the need for physical depletion, and IDO serves as a key regulator of this critical conversion.

The present invention relates to tumor associated antigen (TAA) peptides and to use of same, of polynucleotides encoding same and of cells presenting same as anti-tumor vaccines. More particularly, the present invention relates to tumor associated antigen peptides derived from Uroplakin Ia, Ib, II and III, Prostate specific antigen (PSA), Prostate acid phosphatase (PAP) and Prostate specific membrane antigen (PSMA), BA-46 (Lactadherin), Mucin (MUC-1), and Teratocarcinoma-derived growth factor (CRIPTO-1) and the use of same as anti-tumor vaccines to prevent or cure bladder, prostate, breast or other cancers, carcinomas in particular. Most particularly, the present invention relates to tumor associated antigen peptides which are presentable to the immune system by HLA-A2 molecules.

The present invention describes methods and pharmaceutical compositions for the treatment of cancer in mammals, more particularly in human subjects. More specifically, the invention concerns anti-tumor vaccines based upon plasmid DNA and / or genetic vectors carrying a codon-usage optimized sequence and coding for a mutant form of the ErbB-3 receptor. Furthermore, the invention refers to monoclonal antibodies directed against the ErbB-3 receptor, obtained using these methods and capable to block its activity in cancer cells.

It has been discovered that reducing, inhibiting or preventing the expression of immunosuppressive cytokines or tolergenic agents in antigen presenting cells improves the ability of the antigen presenting cell to promote an immune response. One embodiment provides a genetically engineered antigen presenting cell that has reduced or no expression of IL-10. Preferred antigen presenting cells are dendritic cells. Expression of IL-10 can be inhibited or blocked by genetically engineering the antigen presenting cell to express inhibitory nucleic acids that inhibit or prevent the expression mRNA encoding immunosuppressive cytokines. Inhibitory nucleic acids include siRNA, antisense RNA, antisense DNA, microRNA, and enzymatic nucleic acids that target mRNA encoding immunosuppressive cytokines. Immunosuppressive cytokines include, but are not limited to IL-10, TGF-β, IL-27, IL-35, or combinations thereof. Tolerogenic agents include but are not limited to indoleamine 2,3-dioxygenase.

The invention relates to colon and prostate tumor associated antigen peptides obtainable from prostate specific G protein-coupled receptor (PSGR), six-transmembrane epithelial antigen of prostate (STEAP) and proteins encoded by genes found overexpressed in colon carcinoma cells, such as human 1-8D interferon induced transmembrane protein 2. The invention further relates to a polynucleotide encoding the tumor associated antigen peptides and to pharmaceutical compositions, which are preferably anti-tumor vaccine compositions, containing a tumor associated antigen, at least one tumor associated antigen peptide thereof, or encoding polynucleotide thereof as an active ingredient. The pharmaceutical compositions can be administered to a patient in need thereof to treat or inhibit the development of colon or prostate cancer.

The invention relates to a conjugate of monophosphate A (MPLA) and carbohydrate antigen Globo H and capable of serving as an antitumor vaccine and a preparation method and application thereof. The conjugate can be prepared through a chemical method and has the advantages of definite structure, clear composition and adjuvant needlessness. In addition, the invention further provides the applicationof the conjugate in preparing drug for treating or preventing cancer.

The invention discloses a Thomsen-Friedenreich (TF) antigen and a TF antigen analogue and their chemoenzymatic synthesis method and use. The chemoenzymatic synthesis method comprises the following steps of 1, carrying out chemosynthesis of fluorogalactose and a fluoro-galactosamine analogue, 2, carrying out enzymatic synthesis of a fluoro-TF antigen, and 3, carrying out enzymatic synthesis of a sialyl TF antigen. The preparation method has flexibility of a chemosynthesis method, and high regioselectivity and high efficiency of an enzymatic synthesis method, creatively realizes enzymatic synthesis of the fluoro-TF antigen, and solves the problem that the existing fluoro-TF antigen chemosynthesis method has low substrate reactivity, complex synthesis steps and a low yield. A tumor-associated fluoro-carbohydrate antigen is superior to a natural carbohydrate antigen in pharmacokinetic properties and thus the preparation method has wide application prospects in development of a novel anti-tumor vaccine.

The invention provides a monophosphate A conjugated-Tn anti-tumor vaccine. The monophosphate A conjugated-Tn anti-tumor vaccine is a compound shown in a formula (I), namely Y-L-X(I). The monophosphateA conjugated-Tn anti-tumor vaccine is characterized in that a compound of the second generation of TLR4 ligand I of wholly new structure in the formula (I) is used for replacing MPLA (modified polylactic acid) and coupling with a compound (Tn) with clinical development potential in a formula (II), so as to obtain the two-component vaccine with a clear structure and a stronger anti-tumor function;the anti-tumor application prospect is better.

The invention relates to a preparation method and application of an anti-tumor vaccine based on cell microvesicles and aims to effectively solve problems in preparation of anti-tumor vaccines high inyield, good in universality, strong in killing effect on tumor cells and capable of controlling tumors by improving tumor microenvironments, repairing an immune system and enhancing anti-tumor immuneresponse of organisms. The preparation method comprises the following steps: preparing tumor cell microvesicles loaded with immunomodulators and connecting the surfaces of the microvesicles with adjuvant-loaded liposome to stably form the anti-tumor vaccine. The prepared anti-tumor vaccine is high in yield, good in universality, strong in killing effect on tumor cells and capable of improving tumor microenvironments, repairing an immune system and enhancing anti-tumor immune response of organisms; the method is simple in process and high in efficiency; and the prepared microvesicles are derived from cells, are sufficient in quantity and wide in source, are easy for large-scale production, improve the bioavailability of adjuvants, are effectively applicable to preparation of anti-tumor vaccines based on the cell microvesicles, and can be applied to prevention and treatment of different types of tumors.

The invention discloses a tumor deoxyribonucleic acid (DNA) vaccine taking mucin 1 and survivin as targets and a viral vector vaccine. The invention relates to the field of tumor DNA vaccines and viral vector vaccines, in particular to recombinant DNA vector VR-S8 and VR-MS, recombinant adenovirus Ad-S8 and Ad-MS, and recombinant poxvirus MVA-MS vaccines, and application of the optimum combination of immune ways between DNA vaccines and viral vector vaccines and between the viral vector vaccines in preparing antitumor vaccines.

Provided are novel MUC1 peptides for use in anti-tumor vaccination and methods of producing those peptides. Furthermore, methods of producing a population of autologous antigen presenting cells (APCs) and of producing genetically engineered APCs, which are capable of inducing effective immune responses against MUC1 are described. The described peptides are particularly useful for the treatment of breast cancer or other MUC1-positive carcinomas including colorectal, pancreatic and gastric carcinomas.

The invention relates to a mimic eptitope peptide of BAFF-R and a DNA coding the peptide and the application of the mimic eptitope peptide in the preparation of antitumor bacterins and drugs. The mimic eptitope of 7 amino acids of BAF-R is a mimic eptitope of molecule BAFF-R with high affinity with a monoclonal antibody of BAFF-R, and is obtained through selection from a phage random display 7-peptide bank with a monoclonal antibody of BAFF-R as the antigen, wherein the sequence of the amino acids is Gly Tyr Thr Arg Trp Gly Cys. The 7-amino-acid mimic eptitope can also be used to construct a poly-peptide vaccine. The clonal inhibition rates of the phage display peptide provided by the invention are all more than 50 percent, and can specifically inhibit the combination between antibody and antigen for a larger extent, greatly improve the proliferation of mouse spleen lymphocytes without adjuvant, the mimic antigen is good in immunogenicity, as illustrated by the induced cell immune response after mice are vaccinated with the mimic antigen.

The invention provides an anti-tumor vaccine compound which is prepared by physically mixing ROS-rich cell microvesicle and immune activating agent. The invention provides a preparation method for theanti-tumor vaccine compound. The invention provides an anti-tumor vaccine compound injection. The invention provides an application of the anti-tumor vaccine compound. The anti-tumor vaccine compoundis applied to tumors, such as lung cancer, breast cancer, glioma, ovarian cancer, gastric cancer, colorectal cancer, osteogenic sarcoma, prostatic cancer, cervical cancer, malignant pleural effusionor melanoma. According to the invention, the problems of low immune activation efficiency, inaccuracy and few antigens of the present vaccine can be solved.

The invention discloses an N-acyl group modified sialic acid (alpha-(2-6))-D-amino pyranose derivative and its synthetic method and use. The sialic acid (alpha-(2-6))-D-amino pyranose derivative shown in the formula (I) is synthesized from raw materials of D-galactosamine (glucose) and sialic acid and is coupled with a carrier protein or a polypeptide to form a glycoprotein (glycopeptide) conjugate. In a structure of the N-acyl group modified sialic acid (alpha-(2-6))-D-amino pyranose derivative, a derivative acyl group replaces an acetyl group and thus the structure is novel. The N-acyl group modified sialic acid (alpha-(2-6))-D-amino pyranose derivative has good activity in anti-tumor vaccines. A result of an experiment on mice shows that through structural derivatization, a carbohydrate antigen based vaccine can produce an effective immune response and a mass of antibodies and IgG / IgM is improved obviously. The antibodies can identify specifically tumor cells expressing STn and thus anti-tumor effects are realized. STn antigens can be expressed on multiple tumors and thus the N-acyl group modified sialic acid (alpha-(2-6))-D-amino pyranose derivative has a wide application scope.

The invention relates to a fusion protein TT-B7-H4IgV as well as a preparation method and an application thereof. The B7-H4IgV is a variable region IgV of a B7-H4 molecule extracellular region, TT is a T auxiliary cell epitope peptide or a tetanus toxoid epitope, the N end of the fusion protein TT-B7-H4IgV is connected with 6 His residues, a connection mode is as follows: 6*His-TT-B7-H4IgV, and the fusion protein TT-B7-H4IgV is applied to prepare anti-tumor vaccines which take the B7-H4 as a target spot. The fusion protein TT-B7-H4IgV is established by selecting the B7-H4 as a target spot and taking the TT as antigen presentation and is in accordance with prospects by being identified by a Western blot and checking orders by the Western blot; a purified fusion protein TT-hB7-H4IgV is used for immunizing small Kunming mice, and the biological activity of antiserums is measured by ELISA and flow cytometry so as to prove that a B7-H4 antiserum and the B7-H4 have good combination activity, thus the purified fusion protein TT-hB7-H4IgV can induce organisms to generate anti-B7-H4 polyclonal antibodies.

The invention discloses a recombinant BCG vaccine based on human MUC1 repetitive sequence and GM-CSF fusion expression. Firstly, MUC1 repetitive sequence multimers and fusion genes connected with GM-CSF genes by connecting DNA are constructed, a signal peptide sequence and a Kozak sequence are further connected, and an expression vector is constructed; and the constructed fusion genes are transfected to BCG vaccines, and applied to the preparation of anti-tumor vaccine or anti-tumor medicament by using MUC1 as a target spot. The recombinant BCG vaccine realizes effective combination of antibody, adjuvant and vaccine vector so that the immunogenic property of the MUC1 tumor vaccine achieves more effective and durable effect; and simultaneously the recombinant BCG vaccine is safe, has no toxic and side effects, and can induce specific T cell immune response and durable secretion expression of the human MUC1 repetitive sequence and GM-CSF fusion protein.

The invention provides a glycoconjugate containing STn or F-STn and a preparation method thereof and application for an anti-tumor vaccine, and belongs to the technical field of glycoconjugates. The glycoconjugate containing STn or F-STn comprises STn or F-STn and a vector; STn or F-STn is coupled to the vector through a connecting bond; the connecting bond includes an amido bond or an oxime bondor a C-N bond; the vector includes protein or zwitter-ion polysaccharide or lipid or nucleic acid. The glycoconjugate is applied to preparing an anti-tumor or anti-cancer vaccine or preparing a medicine for improving cell and / or humoral immune response. The vaccine prepared from the glycoconjugate of F-STn can improve humoral immunity and cellular immunologic response, the generated antibody can effectively recognize STn positive tumor cells, and the STn positive tumor cells can be cracked in an ADCC and CDC way.

The invention provides a vaccine and a preparation method thereof. The vaccine comprises bacterial outer membrane vesicles and antigen, wherein the antigen is combined with the bacterial outer membrane vesicles to form nanoparticles. The bacterial outer membrane vesicles are combined with a tumor specific antigen to prepare an anti-tumor vaccine, and an innate immune response and a specific immuneresponse are caused at the same time, so that the target of treating tumors by an autoimmune system of a body is achieved; and the vaccine is high in specificity, small in side effect and has a broadapplication prospect and great market value.

The invention discloses an antitumor vaccine, an encoding gene, an expression vector, an expression engineering bacteria and application of targeted VEGF and mucin1, and belongs to the technical field of biology. An antitumor vaccine fusion protein adopts VEGF165, VEGF165b or corresponding modified VEGF mutants as an epitope vector, at least one section of epitope peptide of tumor related antigen mucin1 is connected to an end N or an end C of the vector to form the antitumor vaccine having a double target effect. The VEGF in the vaccine can be used as the epitope vector to improve the antigenicity of the mucin1 epitope connected with the VEGF, the over-expressed mucin1 tumor cells are killed, the VEGF can also be used as an antigen to produce an antibody for VEGF so as to inhibit the generation of tumor vessels and cut off the nutrient supply of the tumor. Meanwhile, the epitope vector has a heparin-binding domain which can be bond with heparin sepharose, thereby facilitating the subsequent protein purification.

The invention relates to fields of tumor DNA vaccines, viral vector vaccines and protein vaccines and especially relates to a tumor genetically-engineered vaccine utilizing mucin-1 and survivin as target sites. The tumor genetically-engineered vaccine comprises recombinant DNA vectors of CpVR-MS and CpDV-IL2-MS. The invention also relates to a use of recombinant protein vaccines of S8 and 9M, a DNA vaccine, a viral vaccine, a protein vaccine and an optimized combination of immune methods of the DNA vaccine, the viral vaccine and the protein vaccine in preparation of an anti-tumor vaccine.

The invention discloses a synthesis method and an application of a sialylated TF antigen and its fluorination derivatives. The method includes the following steps: (1) chemically synthesizing fluorogalactose and fluorogalactosamine analogues; (2) chemically synthesizing a fluorinated TF antigen; and (3) synthesizing the sialylated TF antigen and its fluorination derivatives through an enzyme technology. The flexibility of a chemical synthesis technology is combined with the high regioselectivity and the high efficiency of the enzyme synthesis technology, so the enzymatic synthesis of the fluorosialylated TF antigen is achieved for the first time, and the disadvantages of many synthesis steps, poor stereoselectivity, low yield and use of a heavy metal salt in existing chemical synthesis ofthe fluorosialylated TF antigen are overcome. A fluorotumor-associated carbohydrate antigen has a higher stability than natural carbohydrate antigen, so the sialylated TF antigen and its fluorinationderivatives have a broad application prospect in the development of novel antitumor vaccines.

The invention relates to the field of tumor DNA vaccines and virus vector vaccines with fibroblast activation protein alpha as a target, in particular to recombinant DNA carrier CpVR-FAP, recombinant adenovirus Ad-FAP and recombinant poxvirus MVA-FAP vaccines, DNA vaccines, virus vector vaccines and optimal combination of immune ways of the virus vector vaccines or application of combination of the vaccines and cyclophosphamide in preparation of anti-tumor vaccines.

The present invention provides novel naturally-processed antigenic peptides which are candidate tumor antigens in melanoma and other tumors. These antigenic peptides are presented by human MHC class II HLA-DR molecules. They originate from the translation factor eIF-4A, the IFN-gamma-inducible protein p78, the cytoskeletal protein vimentin and the iron-binding surface protein melanotransferrin. The antigenic peptides of the present invention can be used as markers in diagnosis of the respective tumors and in therapy as anti-tumor vaccines.