211results about How to "Improve anti-tumor efficacy" patented technology

The present invention concerns methods and compositions for the treatment of cancer and cancer cells using altered poxviruses, including a vaccinia virus that has been altered to generate a more effective therapeutic agent. Such poxviruses are engineered to be attenuated or weakened in their ability to affect normal cells. In some embodiments, methods and compositions involve poxviruses that possess mutations that result in poxviruses with diminished or eliminated capability to implement an antiviral response in a host. Poxviruses with these mutations in combination with other mutations can be employed for more effective treatment of cancer.

The instant invention provides compositions comprising a prodrug, the prodrug comprising a therapeutically active drug; and a peptide selected from the group consisting of the sequences: Ser-Ser-Lys-Tyr-Gln (SEQ ID NO:1);Gly-Lys-Ser-Gln-Tyr-Gln (SEQ ID NO:2); and Gly-Ser-Ala-Lys-Tyr-Gln (SEQ ID NO:3) wherein the peptide is linked to the therapeutically active drug to inhibit the therapeutic activity of the drug, and wherein the therapeutically active drug is cleaved from the peptide upon proteolysis by an enzyme having a proteolytic activity of prostate specific antigen (PSA). The invention further provides methods of making and using the claimed compositions.

The invention belongs to the fields of immunology and cell biology, and relates to a tumor precision T cell containing an efficient killing starting mechanism and an application of the tumor precision T cell, in particular to a CAR (chimeric antigen receptor) having moderate-affinity binding characteristic with a broad-spectrum expression membrane antigen on the tumor cell surface as well as a new-generation tumor precision T cell, namely, Baize T. T cell activation is started rapidly under the action of the CAR having the moderate-affinity binding characteristic, an activation signal of the CAR is superposed with a TCR (T cell receptor) signal with tumor antigen natural recognition capacity in a CTL (tumor-specific cytotoxic T lymphocyte), the CTL is activated to proliferate and grow in a tumor microenvironment, and a tumor cell is killed preciously by the tumor-antigen-specific TCR. The tumor precision T cell has broad anti-tumor application prospect.

The invention relates to a common carrier material based on graphene oxide for a targeting anticancer drug and a gene and application and application. Folic acid, lactobionic acid and other tumor cell targeting or liver targeting molecules and part of amino groups of soluble chitosan are connected by amide bonds to prepare a conjugate, the conjugate is then connected with graphene oxide, quaternization is performed by using an epoxy compound with a quaternary ammonium group, and gene molecules are loaded by the quaternizationquaternized part of the chitosan through electrostatic attraction; and then the anticancer drug is loaded by pi-pi conjugates, hydrogen bonds and hydrophobic effects in a non-covalent bond method. By adopting the targeting performance of targeting molecules and effects of graphene oxide of a particular size to enhance penetration and retention in tumor tissues and combining the performance of the graphene oxide for pH response control release of the loaded drug, the drug can be realized released in a tumor cell, an intelligent delivery system for the common carrier of the tumor targeting or liver targeting anticancer drug and the gene is synthesized from the perspective of synergetic medication, and a theoretical basis and a method basis are provided for combined therapy of tumor.

The invention discloses a method for simultaneous and efficient amplification of CD<3+>CD<56+>CIK cells and CD<3->CD<56+>NK cells. The method comprises the steps as follows: the concentration of separated PBMC (peripheral blood mononuclear cells) is adjusted by a serum-free medium containing autologous plasma, an Anti-CD16 antibody, IL-2 and IL-15 are added, and then the mixture is transferred into a T175 culture flask for culture; an Anti-CD3 antibody and an Anti-CD137 antibody are added; a serum-free medium containing the autologous plasma, IL-2 and IL-15 is supplemented every two days according to the cell growth condition; the cell concentration is controlled to be about 1.5*10<6> / ml; and after culture is performed for 14-21 days, large quantities of high-purity CD<3+>CD<56+>CIK cells and CD<3->CD<56+>NK cells can be obtained simultaneously, and the total cell quantity can reach an effective value of the cell quantity required for adoptive cellular immunotherapy clinically for tumor. The method for simultaneous and efficient amplification of the CD<3+>CD<56+>CIK cells and the CD<3->CD<56+>NK cells is simple, convenient, effective and high in cell killing activity.

The present invention relates generally to the field of generating fusion proteins to be used in cancer therapy, and more specifically, to nucleotide sequences encoding the fusion proteins, wherein the chimeric fusion proteins comprises at least one targeting moiety and at least one immunomodulatory moiety that counteracts the immune tolerance of cancer cells.

The invention belongs to the field of pharmacology, and relates to stapled-RGD polypeptide, and applications thereof in tumor targeting delivery. Multifunctional targeting polypeptide molecule stapled-RGD with high combination activity with integrin and biological membrane barrier penetration capacity is designed and prepared based on binding peptide cyclization technology; and preparation of fluorescein, drugs, and high molecule carriers modified by the multifunctional targeting polypeptide molecule stapled-RGD, and applications of the fluorescein, the drugs, and the high molecule carriers in tumor imaging and construction of targeted therapy targeted drug delivery systems are disclosed. It is shown by results that specific uptaking of model drugs carried by stapled-RGD by positive cells, tumor mimicry vessels, and tumor ball tissues of expressed integrin is realized, higher tumor targeting capacity, imaging functions, and membrane barrier cell penetration capacity are achieved; nano targeted drug delivery systems constructed by the high molecule carriers modified by stapled-RGD can be used for delivering carried model drugs to target tissues, antitumor drug effect is improved obviously; and stapled-RGD possesses a promising application prospect in mediating drugs, nano targeted drug delivery system membrane barrier penetration, active target searching, tumor diagnosis, and targeted therapy.

Provided herein are peptidomimetic macrocycles and methods of using such macrocycles for the treatment of disease.

A compound Cu(DDC)2 with relatively high tumor-inhibiting activity can be used for treating cancers such as melanoma, breast cancer, lung cancer, liver cancer, and the like. The treatment effect is broad, and the compound has certain selective killing effect against tumor cells. The invention relates to an Cu(DDC)2 injection protein nano-particle preparation used for treating tumor, and a preparation method thereof. Therefore, problems of poor water-solubility and difficulty in intravenous administration of Cu(DDC)2 are solved. According to the invention, with an ultrasonic method, a high-pressure homogenization method, and a micro-jet method, the Cu(DDC)2 injection protein nano-particles are prepared. The Cu(DDC)2 protein nano-particles are prepared from the components that (Cu(DDC)2 + organic solvent) :(protein + water) = 1:2-1:30, wherein the specification of Cu(DDC)2 is 0.01-5mg / mL, the specification of protein is 0.05-25% (w / v), and a ratio of organic solvent to water is 1:2-1:30. Proteins such as human serum albumin (HSA), bovine serum albumin (BSA), hydrophobic protein, glycoprotein, and lipoprotein or polypeptide is adopted as a carrier and a stabilizer for coating medicine particles, such that the particles have good biocompatibility and high security. Cu(DDC)2 tumor-inhibiting treatment effect is improved, and adverse reaction is reduced.

The invention belongs to the technical field of biological pharmacy, and relates to a tumor targeting polypeptide-medicine coupling derivative, and a preparation method and application thereof. The tumor targeting polypeptide-medicine coupling derivative comprises targeting polypeptides, long effect polypeptides and medicine molecules, wherein the targeting polypeptides are connected onto the endC of the long effect polypeptides through flexible connecting peptides; fusion peptides are used as carriers of the medicine molecules; the medicine carriers and the long effect polypeptides in the fusion peptides are connected through chemical bonds; and the long effect polypeptides are polypeptide or protein structural domains having the affine mutual effects with human serum albumin. The tumortargeting polypeptide-medicine coupling derivative can be combined with the human serum albumin; the remaining half-life period in the blood circulation system can be obviously prolonged; the long-term effectiveness in the body is realized; the targeting and seepage into the tumor tissues or cells can be realized; then, free effect molecules are released in tumor tissue micro acid environments orin cells in through an acid hydrolysis mechanism; and a better anti-tumor efficiency is achieved.

The invention belongs to the field of pharmaceutic preparation, and relates to a targeted drug-carrying liposome of a tumor associated fibroblast. The surface of the targeted drug-carrying liposome is modified with a high-affinity ligand of a specific expression protein of the tumor associated fibroblast. The targeted drug-carrying liposome is capable of realizing targeted delivering of drugs into the tumor associated fibroblast, realizing intervention on tumor microenvironment via action on the tumor associated fibroblast, and realizing tumor treatment. And in addition, the tumor associated fibroblast targeted preparation can be combined with routine tumor cell targeted nano preparations so as to improve antitumous effects of the routine tumor cell targeted nano preparations.

The preparation provides a nano drug loading system, which is simple is a preparation method, mature in process, stable in property and good in biocompatibility. According to the nano drug loading system, nano particles are coupled to the surfaces of macrophages through maleic amide bonds; the tumor is jointly treated through the immune regulation function of macrophages and the functions of the nanoparticles, so that the anti-tumor curative effect is improved; the problem that in the prior art, drug micromolecules cannot be effectively enriched and targeted at tumor sites is solved, and the nano drug loading system has important application prospects in the nano medical field and the tumor treatment field.

The invention discloses a bionic nano-carrier as well as a preparation method and application thereof, and belongs to the technical field of pharmaceutical preparations. According to the bionic nano-carrier, cationic nanoparticles entrapping a chemotherapeutic drug serve as an inner core, and surfaces of the cationic nanoparticles are coated with a hybrid cell membrane composed of an immune cell membrane and a tumor cell membrane to serve as a shell. The bionic nano-carrier is high in targeting property and strong in uptake capacity, can enhance anti-tumor curative effect, provides a new thought for individualized and accurate treatment, and has relatively high clinical practical significance.

The invention relates to the application of ursolic-acid nano medicine-carrying microspheres for treating tumors. The ursolic-acid nano medicine-carrying microspheres contain ursolic acid and a medicine-carrying material which are mixed, wherein the medicine-carrying material is a biparental segmented copolymer synthesized by one of polycaprolactone, polylactic acid or polyglycolic acid and polyethylene glycol, i.e. polycaprolactone-polyethylene glycol (mPEG-PCL), polylactic acid-polyethylene glycol (mPEG-PLA) or polyglycolic acid-polyethylene glycol (mPEG-PLGA); and the ursolic-acid nano medicine-carrying microspheres comprise 5 to 35wt% of ursolic acid and 65 to 95wt% of medicine-carrying material which are mixed.

The present invention is application of medicine carrying chitosan-fatty acid grafting micelle in preparing targeting antitumor medicine carrier, especially antitumor medicine carrier targeting to lung cancer cell nucleus, cervical carcinoma cell nucleus and mammary cancer cell nucleus. The chitosan-fatty acid grafting micelle of the present invention has grafting carrier with low toxicity, and may be ingested fast by cell nucleus to target to cell nucleus and to raise the curative effect of antitumor medicine by up to 80 times. It has cell nucleus targeting function of permeating cell membrane fast with less destruction by intracellular lysosome. The grafting micelle with hydrophobic kernel can envelop hydrophobic antitumor medicine targeting cell nucleus to form medicine carrying grafting micelle. The present invention provides nanometer subcellular organelle administration for high efficiency low toxicity tumor treatment.

The invention relates to a cabazitaxel lipid microsphere injection and a preparation method thereof. The injection comprises the following components in percentage by weight: 0.01% to 1 % of cabazitaxel cholesterol complex (based on cabazitaxel), 5% to 30% of oil for injection; 1% to 6% of phospholipid for injection, 0.2% to 0.7% of auxiliary emulsifier, 0.05% to 1.0% of amphiphilic polyamino, 2.0% to 3.5% of osmotic pressure modifier, the balance being water for injection. The cabazitaxel lipid microsphere injection is prepared by using phospholipid as an emulsifier, a surfactant as a coemulsifier, and high-purity cabazitaxel as an active ingredient, and adding cholesterol, amphiphilic polyamino acids, an osmotic pressure modifier and water for injection through an ultrahigh pressure microjet nano-dispersion technology. By means of the unique interaction of cholesterol and drugs, the chemical stability of cabazitaxel in lipid microspheres is improved, and the thermodynamic stability of cabazitaxel in the lipid microspheres is also improved. The stability of a preparation is further enhanced by adding the amphiphilic polyamino acids provided by the invention.

The invention discloses folate-conjugated polyethylene glycol monostearate, and a preparation method and application thereof. The folate-conjugated polyethylene glycol monostearate has a structure shown as below, wherein n equals to 45-136. The preparation method of the folate-conjugated polyethylene glycol monostearate comprises the following steps: weighing folic acid and triethylamine; adding dimethylsulfoxide for dissolution; adding dicyclohexylcarbodiimide and N-hydroxy succinimide; stirring at room temperature by avoiding light; standing for overnight; filtering to remove by-products; then adding polyethylene glycol monostearate; heating to dissolve; reacting overnight to obtain a coarse product; placing the coarse product in a dialysis bag; dialyzing with water; and conducting freeze-drying to obtain the folate-conjugated polyethylene glycol monostearate. The folate-conjugated polyethylene glycol monostearate can be applied to preparation of a folic acid modified antitumor drug delivery system, improve drug targeting, efficacy and pharmacokinetics, and reduce toxicity.

The present invention relates generally to the field of generating recombinant chimeric fusion proteins to be used in the cancer therapy, and more specifically, to fusion molecules of Anti-EGFR1-TGFβRII, Anti-EGFR1-PD1 and Anti-CTLA4-PD1 and methods of generating same, wherein the methods reduce production costs and increase homogeneity of the recombinant chimeric fusion proteins.

The invention relates to a folic acid-mediated (polyethylene glycol) PEG-graphene oxide doxorubicine-loaded nanoparticle and a preparation method thereof. The preparation method includes carrying out functional modification on graphene oxide with folic acid and PEG, and loading a model drug doxorubicine. According to the invention, the drug loading capacity of the nanoparticle is increased, drug targeting property is improved, and the half-life of plasma and mean residence time are remarkably prolonged, so as to improve the curative effect of doxorubicine. The invention can reduce the toxic and side effects of doxorubicine, and prolong the drug resistance time and improve drug targeting property, so as to enhance the antitumor effect of doxorubicine. The invention has important clinical significance for some medicaments with wide antitumor spectrum but severe adverse effect and high toxicity.

The invention provides a triphenylphosphine-stearic acid grafted chitosan drug-loading micelle. The triphenylphosphine-stearic acid grafted chitosan drug-loading micelle is prepared through a two-stepamide method as follows: grafting tetracarboxybutyl triphenylphosphine to stearic acid grafted chitosan to obtain triphenylphosphine-stearic acid grafted chitosan having a mitochondrion targeting function; and performing coating of an antitumor drug amycin through a dialysis method to obtain the mitochondrion-targeting triphenylphosphine-stearic acid grafted chitosan drug-loading micelle. The drug-loading micelle provided by the invention has an efficient mitochondrion targeting function, and the coated drug amycin can maximally reduce the leakage of the amycin in normal tissues and non-target parts, thereby reducing the toxic or side effect; and meanwhile, a large amount of amycin can be accurately delivered to tumor cell mitochondria in a targeting manner, so that the concentration of the amycin in the tumor cell mitochondria is increased, apoptosis of the tumor cells is induced, and the antitumor curative effect is greatly improved.

The present invention relates to a combination comprising at least fusion protein comprising a binding protein specifically recognizing a cancer-related antigen and an inflammatory cytokine, and a chimeric antigen receptor (CAR)-T cell recognizing a cancer-related antigen.

The invention belongs to the technical field of medicines and relates to a prodrug of an antitumor medicament as well as a preparation method and application thereof. The prodrug is prepared by connecting vitamin E and the antitumor medicament by virtue of a chemical bond. The chemical bond is one of a sulfide bond, an ester bond, an interval disulfide bond and a hydrazone bond. The antitumor medicament is one of paclitaxel and docetaxel. The prodrug of the antitumor medicament and a pharmaceutically acceptable carrier can be prepared into a clinically acceptable dosage form for injection or oral administration, including lipidosome, an emulsion, a lipid microsphere and a PLGA (Poly(Lactic-co-Glycolic Acid) nanoparticle or microsphere. According to the prodrug and the preparation, the activity of the antitumor medicament can be obviously improved, the toxicity is reduced and the development of the preparation is facilitated.

The invention discloses application of cyclic dinucleotide cGAMP to prevention and treatment of tumors through drug combination, belonging to the technical field of biological medicine. The invention also discloses a plurality of drug compositions for prevention and treatment of tumors. The drug compositions for prevention and treatment of tumors are composed of cyclic dinucleotide and one selected from a group consisting of fluorouracil, cyclophosphamide, methotrexate, cisplatin, carboplatin, paclitaxel, vincristine, mitomycin, gemcitabine and actinomycin. Results of in-vivo research show that the drug compositions composed of cyclic dinucleotide and one selected from a group consisting of fluorouracil, cyclophosphamide, methotrexate, cisplatin, carboplatin, paclitaxel, vincristine, mitomycin, gemcitabine and actinomycin have obviously improved curative effect and obviously decreased toxicity.

The invention discloses a docetaxel nanometer micelle, a preparation method and application of the micelle to prepare medicines for treating tumor or drug-resistant tumor. The docetaxel nanometer micelle comprises 1 part by weight of docetaxel, 10-100 parts by weight of a carrier material and 0-10 parts of oil, wherein the average particle size of the docetaxel nanometer micelle is 10-200 nm. According to the preparation, the water solubility of docetaxel is substantially improved, the stability of the preparation is improved, the cycling time of docetaxel in blood is prolonged, the toxic and side effects of conventional preparations are reduced, docetaxel nanometer micelle can be driven to be targeted to tumor tissue through EPR effect, so that the anti-tumor curative effect of docetaxel is improved, and the docetaxel nanometer micelle overcomes the multidrug resistance of tumor.

The present invention discloses a preparation method and uses of an anti-cancer drug estrogen targeting PEG-modified liposome. The liposome preparation method comprises: synthesizing estrone-pegylated phospholipid from activated estrone, taking 40-80 parts by weight of phospholipid, 5-45 parts by weight of cholesterol, and 5-40 parts by weight of pegylated phospholipid, dissolving in methanol, carrying out rotary evaporation, adding an ammonium sulfate aqueous solution, carrying out dialysis, adding 0.5-10 parts by weight of mitoxantrone, carrying out incubation, carrying out dialysis, adding 0.1-20 parts by weight of the estrone-pegylated phospholipid, carrying out incubation, and filtering with a membrane to obtain the liposome preparation. Compared with the liposome in the prior art, the obtained estrogen targeting PEG-modified liposome has characteristics of high encapsulation efficiency, uniform particle size, pharmacokinetics improving, anti-tumor efficacy enhancing, toxicity reducing, simple preparation process and easy scale-up production, and is expected to become the novel pharmaceutical preparation for cancer therapy. The uses are targeted treatments of breast cancer, leukemia and other cancers.

The instant invention provides compositions comprising a prodrug, the prodrug comprising a therapeutically active drug; and a peptide selected from the group consisting of the sequences: Ser-Ser-Lys-Tyr-Gln (SEQ ID NO:1);Gly-Lys-Ser-Gln-Tyr-Gln (SEQ ID NO:2); and Gly-Ser-Ala-Lys-Tyr-Gln (SEQ ID NO:3) wherein the peptide is linked to the therapeutically active drug to inhibit the therapeutic activity of the drug, and wherein the therapeutically active drug is cleaved from the peptide upon proteolysis by an enzyme having a proteolytic activity of prostate specific antigen (PSA). The invention further provides methods of making and using the claimed compositions.

The invention discloses a brain targeted medicine lipidosome preparation as well as a preparation method and an application thereof. The brain targeted medicine lipidosome which has an enhancement effect is prepared by taking oligopeptide with arginine residues as a target molecule and by using a thin film hydration method and a three-bottle method, and the technical problems that a conventional lipidosome preparation cannot penetrate through blood brain barrier and has no brain targeting are solved. The galenic pharmacy observation shows that the encapsulation efficiency and the particle size of the brain targeted medicine lipidosome preparation disclosed by the invention meet the medicine requirements, and compared with ordinary lipidosome, the brain targeted medicine lipidosome disclosed by the invention is good in acid sensitivity and good in stability in serum, and has in-vitro cell medicine effect and in-vivo mouse glioma medicine effect which are higher than those of long circulation Doxorubicin lipidosome.

The present invention relates to Chinese medicine, and is especially one kind of tongue dropping medicine pill for diminishing inflammation and detoxicating. The tongue dropping medicine pill for diminishing inflammation and detoxicating is prepared with saffron, safflower, realgar, toad cake, frankincense and other 16 kinds of Chinese medicinal materials. The medicine of the present invention has the functions of clearing away heat, diminishing inflammation, cooling blood, detoxicating, eliminating swelling, etc. and has high clinical effective rate and low toxicity.

The invention discloses a multifunctional targeting drug delivery system with combined action of chemotherapy and phototherapy and a preparation method thereof. The method comprises the following steps: preparation of drug-loaded nanoparticles; synthesis of HA-NH2; synthesis of DOX-ss-HA-NH2; and preparation of a targeting drug delivery system Ce6@PDA-HA-ss-DOX. The multifunctional targeting drugdelivery system disclosed by the invention has good biocompatibility, biodegradability and low toxicity, and can respond to the biological characteristics of low pH environment, high glutathione concentration and high CD44 receptor expression of tumor cells to release drugs. The chemotherapy is carried out together with photothermal therapy and photodynamic therapy so as to obviously improve the killing effect on the tumor cells, and to provide a better treatment method for tumor.