30results about How to "Efficient and specific killing" patented technology

The invention belongs to the technical field of anticancer drugs, and particularly discloses a manganese dioxide / glucose oxidase @ hyaluronic acid composite anticancer material. The composite anticancer material comprises a core and a shell covering the core, wherein the core comprises a manganese dioxide nanosheet and glucose oxidase modified on the surface of the manganese dioxide nanosheet; andthe shell is hyaluronic acid. The invention further provides preparation and an application of the anticancer material. Studies find that the composite material can effectively and synergistically improve selectivity of cancer cells and normal cells, efficiently and specifically kill the cancer cells, and induce apoptosis of many cancer cells at a low dose through synergy of innovative componentsand composite morphology of the components; and in addition, the material does not influence metabolism of the normal cells basically and has small toxic and side effects.

The present invention provides a single-chain antibody targeting HER2, the single-chain antibody targeting HER2 comprises an amino acid sequence shown in SEQ ID NO: 1. The present invention also provides a chimeric antigen receptor T cell comprising the single-chain antibody targeting HER2, wherein the chimeric antigen receptor targeting HER2 can specifically target HER2, the expansion of T cellsin patients is promoted, the tumor cells can be efficiently and specifically killed, the chimeric antigen receptor T cell has lasting cell viability and lethality, and damage is hardly generated on the normal cells. The invention also provides a preparation method and an application of the chimeric antigen receptor T cell targeting HER2.

The invention provides a preparation method of PD1-knockout chimeric antigen receptor T cell targeting ROR1. The method comprises: linking an encoding gene of the chimeric antigen receptor CAR-ROR1 toa vector, and constructing the recombinant lentivirus, performing transfection on CD3 positive T lymphocytes, and performing knockout of the PD1 gene of the transfected T cells to obtain the PD1-knockout chimeric antigen receptor T cell targeting ROR1. The knockout of the PD1 gene by the chimeric antigen receptor T cell is in favor of amplification of T cells in the patient, and avoids the escapeof immunosurveillance of the tumor cells, the T cell has the performance of killing tumor cells with high efficiency and specificity, which maintains the viability and lethality of the cells for a long time and does not cause damage to normal cells.

The present invention provides a single-chain antibody targeting ROR1, the single-chain antibody targeting ROR1 comprises an amino acid sequence shown in SEQ ID NO: 1. The present invention also provides a chimeric antigen receptor T cell comprising the single-chain antibody targeting ROR1, wherein the chimeric antigen receptor targeting ROR1 can specifically target ROR1, the cellular immunity effect of T cells can be activated, the ROR1 positive tumor cells can be efficiently and specifically killed, the chimeric antigen receptor has lasting cell vitality and lethality, and damage is hardly generated on the normal cells. The invention also provides a preparation method and an application of the chimeric antigen receptor T cell targeting ROR1.

The present invention provides a single-chain antibody targeting CD22, the single-chain antibody targeting CD22 comprises an amino acid sequence shown in SEQ ID NO: 1, and the single-chain antibody targeting CD22 is a humanized single-chain antibody. The present invention also provides a chimeric antigen receptor T cell comprising the single-chain antibody targeting CD22, wherein the chimeric antigen receptor targeting CD22 can specifically target CD22, especially can be targeted to tumor cells that do not express CD19, the expansion of T cells in patients is promoted, and the tumor cells canbe efficiently and specifically killed. In addition, the chimeric antigen receptor T cell targeting CD22 produced by humanized single-chain antibody has better cell viability and lethality. The invention also provides a preparation method and an application of the chimeric antigen receptor T cell targeting CD22.

The present invention provides a single-chain antibody targeting CD19, the single-chain antibody targeting CD19 comprises an amino acid sequence shown in SEQ ID NO: 1, and the single-chain antibody targeting CD19 is a humanized single-chain antibody. The present invention also provides a chimeric antigen receptor T cell comprising the single-chain antibody targeting CD19, wherein the chimeric antigen receptor targeting CD19 can specifically target CD19 on tumor cells, the expansion of T cells in patients is promoted, and the tumor cells can be efficiently and specifically killed. In addition,the chimeric antigen receptor T cell targeting CD19 produced by humanized single-chain antibody has better cell viability and lethality. The invention also provides a preparation method and an application of the chimeric antigen receptor T cell targeting CD19.

The invention provides a targeting T lymphocyte. The targeting T lymphocyte comprises a chimeric antigen receptor CAR-CD38 targeting CD38 and / or a chimeric antigen receptor CAR-BCMA targeting BCMA. The targeting T lymphocyte has wide and high targeting identifiability on tumor cells, target spot escape of the tumor cells can be avoided, the tumor cells are efficiently and specifically killed, andthe broad-spectrum destruction of the targeting T lymphocyte is enhanced. The invention further provides a preparation method and application of the targeting T lymphocyte.

The invention provides a preparation method of a PD1-knockout chimeric antigen receptor T cell targeting CD317. The method comprises: linking an encoding gene of the chimeric antigen receptor CAR-CD317 and targeting CD317 to a vector, and constructing the recombinant lentivirus, performing transfection on CD3 positive T lymphocytes, and performing knockout of the PD1 gene of the transfected T cells to obtain the PD1-knockout chimeric antigen receptor T cell targeting CD317. The knockout of the PD1 gene is carried out by the chimeric antigen receptor T cell, which is in favor of amplification of T cells in the patient, and avoids the escape of immunosurveillance of the tumor cells, and the T cell has the performance of killing CD317 positive tumor cells with high efficiency and specificity,which maintains the viability and lethality of the cells for a long time and does not cause damage to normal cells.

The invention provides a targeting T lymphocyte. The targeting T lymphocyte comprises a chimeric antigen receptor CAR-EGFRvIII targeting EGFRvIII and a chimeric antigen receptor CAR-IL13Ralpha2 targeting IL13Ralpha2, the CAR-EGFRvIII can specifically target the EGFRvIII, the CAR-IL13Ralpha2 can specifically target the IL13Ralpha2, a signal area in a T cell is activated, amplification of the T cellin the body of a patient is promoted, tumor cells are efficiently and specifically killed, escape of the tumor cells can be effectively avoided, and the activity and killing capacity of the cells canbe better maintained. The invention further provides a preparation method and application of the targeting T lymphocyte.

The invention provides a PSMA-targeting single-strand antibody. The PSMA-targeting single-strand antibody comprises an amino acid sequence as shown in SEQ ID NO:1. The invention further provides a chimeric antigen receptor T cell including the PSMA-targeting single-strand antibody. The PSMA-targeting chimeric antigen receptor can specifically target PSMA positive tumor cells and activate T cells to exert cellular immunity effects to realize efficient and specific killing on the PSMA positive tumor cells, has persistent cell viability and lethality, and cannot damage normal cells. The inventionfurther provides a preparation method and application of the PSMA-targeting chimeric antigen receptor T cell.

The invention provides a CD317-targeting chimeric antigen receptor T cell. The CD317-targeting chimeric antigen receptor T cell comprises CD317-targeting chimeric antigen receptor CAR-CD317, the CAR-CD317 comprises amino acid sequences of a CD317-targeting single-chain antibody, an extracellular hinge region, a transmembrane region and an intracellular signal region which are sequentially connected from an amino terminal to a carboxyl terminal, the CD317-targeting single-chain antibody comprises an amino acid sequence shown in SEQ ID NO:1, the intracellular signal region comprises a CD27 signal region and a CD3zeta signal region, and the CD27 signal region comprises an amino acid sequence shown in SEQ ID NO:2. The CAR-CD317 can specifically target CD317 promote amplification of the T cellin a patient and efficiently and specifically kill tumor cells. The invention also provides a preparation method and an application of the T cell.

The present invention provides a single-chain antibody targeting CD20, the single-chain antibody targeting CD20 comprises an amino acid sequence shown in SEQ ID NO: 1, and the single-chain antibody targeting CD20 is a humanized single-chain antibody. The present invention also provides a chimeric antigen receptor T cell comprising the single-chain antibody targeting CD20, wherein the chimeric antigen receptor targeting CD20 can specifically target CD20, especially can be targeted to tumor cells that do not express CD19, the expansion of T cells in patients is promoted, and the tumor cells canbe efficiently and specifically killed. In addition, the chimeric antigen receptor T cell targeting CD20 produced by humanized single-chain antibody has better cell viability and lethality. The invention also provides a preparation method and an application of the chimeric antigen receptor T cell targeting CD20.

The invention provides a chimeric antigen receptor (CAR) CAR-EGFR targeting an epidermal growth factor receptor (EGFR). The CAR-EGFR comprises an amino acid sequence shown as SEQ ID NO:1. The invention further provides CAR-T cells comprising the CAR-EGFR. The CAR-EGFR targeting the EGFR can specifically target EGFR positive tumor cells, activates the T cells to play a cellular immune role, efficiently and specifically kills the EGFR positive tumor cells, has long-lasting cellular vitality and lethality, and does not damage normal cells. The invention further provides a preparation method and application of the CAR-T cells targeting the EGFR.

The invention provides a preparation method of a PD1-knockout chimeric antigen receptor T cell targeting HER2. The method comprises: linking an encoding gene of the chimeric antigen receptor CAR-HER2to a vector, and constructing the recombinant lentivirus, performing transfection on CD3 positive T lymphocytes, and performing knockout of the PD1 gene of the transfected T cells to obtain the chimeric antigen receptor T cell targeting HER2. The knockout of the PD1 gene is carried out by the chimeric antigen receptor T cell, which is in favor of amplification of T cells in the patient, and avoidsthe escape of immunosurveillance of the tumor cells, and the T cell has the performance of killing tumor cells with high efficiency and specificity, which maintains the viability and lethality of thecells for a long time and does not cause damage to normal cells.

The present invention provides a single-chain antibody targeting DR5. The single-chain antibody targeting the DR5 comprises an amino acid sequence shown as SEQ ID NO:1. The present invention also provides chimeric antigen receptor T cells comprising the single-chain antibody targeting the DR5. Chimeric antigen receptors targeting the DR5 can specifically target the DR5, promote T cell proliferation in patient body, efficiently and specifically kill tumor cells, better maintain cell viability and lethality, and also do not cause damages on normal cells. The present invention also provides a preparation method and an application of the chimeric antigen receptor T cells targeting the DR5.

The invention provides an EGFR-targeting chimeric antigen receptor CAR-EGFR. The CAR-EGFR comprises an amino acid sequence as shown in SEQ ID NO:1. The invention further provides a chimeric antigen receptor T cell including the CAR-EGFR. The EGFR-targeting chimeric antigen receptor CAR-EGFR can specifically target EGFR positive tumor cells and activate T cells to exert cellular immunity effects torealize efficient and specific killing on the EGFR positive tumor cells, has persistent cell viability and lethality, and cannot damage normal cells. The invention further provides a preparation method and application of the EGFR targeted chimeric antigen receptor T cell.

The invention provides a FGFR4-targeting single-chain antibody. Amino acid sequences of the FGFR4-targeting single-chain antibody comprises at least one kind of of the following sequences of (a) an amino acid sequence of a single-chain antibody heavy chain VH as shown in SEQ ID NO: 1 and an amino acid sequence of a single-chain antibody light chain VL as shown in SEQ ID NO: 2; and (b) an amino acid sequence of a single-chain antibody heavy chain VH as shown in SEQ ID NO: 3 and an amino acid sequence of a single-chain antibody light chain VL as shown in SEQ ID NO: 4. The invention also provides a chimeric antigen receptor and a chimeric antigen receptor T cell which comprise the FGFR4-targeting single-chain antibody. According to the chimeric antigen receptor and the chimeric antigen receptor T cell, FGFR4 can be specifically targeted, the in-vivo amplification of T cell is promoted, tumor cells are efficiently and specifically killed, the activity and lethality of cells are well maintained, and normal cells are not damaged.

The invention provides a method for preparing TCR knockout T cell receptor gene-modified T cells targeting NY-ESO-1, which comprises the following steps: by knocking out the TCR gene on T lymphocytesand preparing T cell receptors targeting NY-ESO-1, and the TCR knockout T cell receptor gene-modified T cell targeting NY-ESO-1 is obtained. The TCR knockout T cell receptor gene-modified T cell targeting NY-ESO-1 can effectively prevent the mismatch of endogenous and exogenous TCR alpha-chain and beta-chain existing in T cells, autoimmune responses are avoided, and efficient and specific killingperformance of NY-ESO-1 positive tumor cells can be kept. The method also provides an application of the TCR knockout T cell receptor gene-modified T cells targeting NY-ESO-1.

The invention discloses a nano-drug based on a terminal lipoyl-containing star polymer. A side chain lipoyl-containing star polymer is obtained by esterification reaction; LA substitution degree controllability has excellent biocompatibility and can be used for controlling a drug release system; a prepared cancer-targeting reduction sensitive reversible cross-linked polymer nanoparticle nano-drugsupports an in vivo stable long cycle, is enriched in cancer tissues, efficiently enters cells, and quickly decrosslinks in the cells to release the drug; cancer cells are efficiently and specificallykilled, so that toxic or side effects caused by growth of the cancers are effectively inhibited.

The invention provides a preparation method PD1-knockout chimeric antigen receptor T cell targeting EGFR. The method comprises: linking an encoding gene of the chimeric antigen receptor CAR-EGFR and targeting EGFR to a vector, and constructing the recombinant lentivirus, performing transfection on CD3 positive T lymphocytes, and performing knockout of the PD1 gene of the transfected T cells to obtain the PD1-knockout chimeric antigen receptor T cell targeting EGFR. The knockout of the PD1 gene is realized by the chimeric antigen receptor T cell, which is in favor of amplification of T cells inthe patient, and avoids the escape of immunosurveillance of the tumor cells, and the T cell has the performance of killing tumor cells with high efficiency and specificity, which does not cause damage to normal cells. At the same time, the chimeric antigen receptor T cell targeting EGFR prepared by a humanized single-chain antibody can better maintain the viability and lethality of chimeric antigen receptor T cells.

The invention belongs to the technical field of biomedicine, and relates to an infectious disease and tumor complication immune technology, in particular to a preparation method and application of a CAR-T cell with HIV-1 gp120 and CD20 as double targets. The invention also provides a lentiviral vector based on the combination of a chimeric antigen receptor of a widely neutralizing antibody 3BNC117 and an anti-CD20 chimeric antigen receptor. The chimeric antigen receptor disclosed by the invention comprises a single-chain antibody ScFv targeting HIV-1 gp120, an IgG4 hinge region, a CD8 transmembrane region, 4-1BB and a zeta chain of a leukocyte antigen differentiation group 3. Tests show that the double-target CAR-T cell can efficiently and specifically remove HIV infected cells and lymphoma cells, is used for preparing drugs and reagents for treating AIDS-related lymphoma, and has a good application prospect.

The invention discloses a preparation method of a star-shaped polymer containing lipoyl at the tail end and a preparation method of polymer nanoparticles. The star-shaped polymer with the side chain containing lipoyl is obtained through esterification reaction, has controllable LA substitution degree , excellent biocompatibility, and can be used for controlling a drug release system by using the star-shaped polymer; the prepared cancer-targeted reduction-sensitive reversibly-crosslinked polymer nanoparticle nano-drug can be in in-vivo stable long circulation, is highly enriched in cancer tissues, efficiently enters cells, is rapidly decrosslinked in the cells, releases the drug, to efficiently and specifically kill cancer cells, thus effectively inhibiting the growth of cancer and having no toxic or side effect.

The invention discloses a nano-drug based on a terminal lipoyl-containing star polymer. A side chain lipoyl-containing star polymer is obtained by esterification reaction; LA substitution degree controllability has excellent biocompatibility and can be used for controlling a drug release system; a prepared cancer-targeting reduction sensitive reversible cross-linked polymer nanoparticle nano-drugsupports an in vivo stable long cycle, is enriched in cancer tissues, efficiently enters cells, and quickly decrosslinks in the cells to release the drug; cancer cells are efficiently and specificallykilled, so that toxic or side effects caused by growth of the cancers are effectively inhibited.

The invention discloses a CD276-targeting chimeric antigen receptor with CD28 and 4-1BB as costimulatory structural domains and application of the CD276-targeting chimeric antigen receptor, and belongs to the technical field of biological medicine. According to the CD276-targeting chimeric antigen receptor T cell disclosed by the invention, CD28 and 4-1BB are taken as costimulatory structural domains, so that the CD276-targeting chimeric antigen receptor T cell has strong killing activity on positive tumor cell lines expressing CD276, has stronger killing activity and durability in vivo, and is beneficial to the generation of memory phenotype T cells. In-vitro function tests show that the CD276-targeted chimeric antigen receptor T cell has killing activity on CD276 positive liver cancer cell lines.

The invention discloses a star polymer with a terminal containing lipoyl, a preparation method thereof, polymer nanoparticles prepared from the star polymer, and applications of the star polymer. Thestar polymer with side chains containing lipoyl is prepared through esterification reaction; the LA substitution degree is controllable; excellent biocompatibility is achieved; the star polymer is used for controlling drug release systems; the reduction sensitive reversibly crosslinked polymer nanoparticle nanometer medicine which is prepared from the star polymer and possesses cancer targeting performance is used for supporting in vivo stable long cycle; enrichment in cancer tissues is realized; high efficiency entering into cells is realized; rapid de-crosslinking in cells is realized; release of drugs is realized; high efficiency killing of cancer cells with specificity is realized; growth of cancer is inhibited effectively without causing toxic or side effect.

The invention discloses a star-shaped polymer containing a lipoyl group at the end, a preparation method thereof, polymer nanoparticles prepared therefrom and applications thereof. The star-shaped polymer containing lipoyl group in the side chain is obtained by esterification. The degree of LA substitution is controllable and has excellent biocompatibility. It can be used to control the drug release system, and the prepared cancer-targeted reduction-sensitive reversible cross-linked polymer Nano-particles and nano-drugs support stable long-term circulation in the body, but are highly enriched in cancer tissues and efficiently enter cells, quickly de-crosslink and release drugs in cells, efficiently and specifically kill cancer cells, and effectively inhibit the growth of cancer without causing toxic side effects.

The present invention provides a chimeric antigen receptor targeting EGFRvIII with high affinity. The chimeric antigen receptor is mutated from a commonly used chimeric antigen receptor targeting EGFRvIII. Its amino acid sequence is as shown in SEQ ID NO:1 shown. The present invention also provides a cord blood nucleated cell containing the chimeric antigen receptor, which can efficiently target the EGFRvIII antigen through the chimeric antigen receptor, has a stronger ability to kill EGFRvIII-positive tumor cells, and can be used to prepare prophylactic and Drugs for the treatment of a variety of EGFRvIII-positive tumors.

The invention provides a preparation method of a PD1-knockout chimeric antigen receptor T cell targeting DR5. The method comprises: linking an encoding gene of the chimeric antigen receptor CAR-DR5 and targeting DR5 to a vector, and constructing the recombinant lentivirus, performing transfection on CD3 positive T lymphocytes, and performing knockout of the PD1 gene of the transfected T cells to obtain the PD1-knockout chimeric antigen receptor T cell targeting DR5. The knockout of the PD1 gene is carried out by the chimeric antigen receptor T cell, which is in favor of amplification of T cells in the patient, and avoids the escape of immunosurveillance of the tumor cells, and the T cell has the performance of killing tumor cells with high efficiency and specificity, which maintains the viability and lethality of the cells for a long time and does not cause damage to normal cells.

The invention provides a FGFR4-and-DR5-targeting chimeric antigen receptor T cell as well as a preparation method and application thereof. The chimeric antigen receptor T cell comprises a FGFR4-targeting himeric antigen receptor CAR-FGFR4 and a DR5-targeting chimeric antigen receptor CAR-DR5; the CAR-FGFR4 comprises a FGFR4-targeting single-chain antibody, an extracellular hinge region, a transmembrane region and an intracellular signal region which are sequentially connected from an amino terminal to a carboxyl terminal; the CAR-DR5 comprises a DR5-targeteing single-chain antibody, an extracellular hinge region, a transmembrane region and an intracellular signal region which are sequentially connected from an amino terminal to a carboxyl terminal; and the FGFR4-targeting single-chain antibody comprises at least one kind of the following components of (a) a single-chain antibody heavy chain VH as shown in SEQ ID NO: 1 and a single-chain antibody light chain VL as shown in SEQ ID NO: 2; and (b) a single-chain antibody heavy chain VH as shown in SEQ ID NO: 3 and a single-chain antibody light chain VL as shown in SEQ ID NO: 4.

The invention provides a high-affinity chimeric antigen receptor targeting EGFRvIII, the chimeric antigen receptor is formed by mutation of a chimeric antigen receptor commonly used at present and targeting EGFRvIII, and the amino acid sequence of the chimeric antigen receptor is shown as SEQ ID NO: 1. The invention further provides an umbilical cord blood karyocyte containing the chimeric antigenreceptor, which can efficiently target an EGFRvIII antigen through the chimeric antigen receptor, has stronger capability of killing EGFRvIII positive tumor cells, and can be used for preparing medicines for preventing and treating various EGFRvIII positive tumors.