38results about How to "Eliminates the possibility of self-replication" patented technology

The invention discloses a CAR-T transgene vector based on replication defective recombinant lentivirus. The CAR-T transgene vector comprises an original nuclear replicon pUCOri sequence, a resistance gene AmpR sequence containing ampicillin, a virus replicon SV40 Ori sequence, a lentivirus packaging cis element, ZsGreen1 green fluorescent protein, an IRES ribosome binding sequence, a human EF1 alpha promoter , a chimeric antigen receptor of second-generation CAR or third-generation CAR and a regulating element, wherein the original nuclear replicon pUCOri sequence is used for plasmid replication; the resistance gene AmpR sequence is used for massively proliferating target strains; the virus replicon SV40 Ori sequence is used for enhancing replication in eukaryocyte; the lentivirus packaging cis element is used for lentivirus packaging; the ZsGreen1 green fluorescent protein is used for expressing green fluorescent for eukaryocyte; the IRES ribosome binding sequence is used for jointly transcribing and expressing protein; the human EF1 alpha promoter is used for conducting eukaryotic transcription on antigen receptor genes; the chimeric antigen receptor is used for forming the second-generation CAR or the third-generation CAR integrating recognition, transfer and start; the regulating element is used for enhancing expression efficiency of transgenes and used after eWPRE-enhanced type woodchuck hepatitis b virus is transcribed. Besides, the invention further discloses a construction method and application of the vector. By means of the CAR-T transgene vector and the construction method and application of the vector, secretion of cell factors and an in vitro killing effect of CAR-T cells can be remarkably improved, and the clinical treatment effect is remarkable.

The invention discloses an anti-HER2 chimeric antigen receptor, an encoding gene, a recombinant expression vector, a construction method of the recombinant expression vector, and an application. The anti-HER2 chimeric antigen receptor comprises CD8 leader chimeric receptor signal peptide, an HER2 single-chain antibody heavy chain VH, Optimal Linker C, an HER2 single-chain antibody light chain VL, a CD8 Hinge chimeric receptor hinge, a CD8 Transmembrane chimeric receptor transmembrane domain, a CD137 chimeric receptor co-stimulated factor and a TCR chimeric receptor T cell activating domain which are connected in series. Moreover, the invention discloses an encoding gene of the anti-HER2 chimeric antigen receptor, a recombinant expression vector, a construction method of the recombinant expression vector, and an application. Secretion of cell factors and an in-vitro killing effect of CAR-T cells are obviously improved, and the CAR-T cells have an outstanding clinical treatment effect.

The invention discloses an anti-BCMA chimeric antigen receptor, an encoding gene, a recombinant expression vector and an establishing method and application of the anti-BCMA chimeric antigen receptor, the encoding gene and the recombinant expression vector. The receptor comprises a CD8 leader chimeric receptor signal peptide, a BCMA single-chain antibody heavy chain VH, an Optimal Linker C, a BCMA single-chain antibody light chain VL, a CD8 Hinge chimeric receptor hinge, a CD8 Transmembrane chimeric receptor transmembrane domain, a CD137 chimeric receptor co-stimulatory factor and a TCR chimeric receptor T cell activating domain which are sequentially connected in series. In addition, the invention further discloses the encoding gene and the recombinant expression vector of the anti-BCMA chimeric antigen receptor and the establishing method and application of the encoding gene and the recombinant expression vector. The secretion of cell factors and the cytotoxicity in vitro of CAR-T cells can be remarkably improved, and the clinical treatment effect is outstanding.

The invention discloses an anti-CD138 chimeric antigen receptor, a coding gene, a recombinant expression vector and a construction method and an application of the recombinant expression vector. The anti-CD138 chimeric antigen receptor comprises a CD8leader chimeric receptor signal peptide, a light chain VH of the CD138 single-chain antibody, an Optimal Linker C, a heavy chain VL of a CD138 single-chain antibody, a CD8Hinge chimeric receptor hinge, a CD8Transmembrane chimeric receptor transmembrane domain, a CD137 chimeric receptor co-stimulation factor and a TCR chimeric receptor T-cell activation domain, which are serially connected in sequence. In addition, the invention discloses the coding gene of the anti-CD138 chimeric antigen receptor, the recombinant expression vector and the construction method and the application of the recombinant expression vector. According to the anti-CD138 chimeric antigen receptor, the secretion of cell factors and the in vitro killing effect of CAR-T (Chimeric Antigen Receptor T-Cell Immunotherapy) cells can be remarkably improved, and the clinical treatment effect is outstanding.

The invention discloses an anti-EGFRvIII chimeric antigen receptor, an encoding gene, a recombinant expression vector, a construction method of the recombinant expression vector, and an application. The anti-EGFRvIII chimeric antigen receptor comprises CD8 leader chimeric receptor signal peptide, an EGFRvIII single-chain antibody light chain VL, Optimal Linker C, an EGFRvIII single-chain antibody heavy chain VH, a CD8 Hinge chimeric receptor hinge, a CD8 Transmembrane chimeric receptor transmembrane domain, a CD137 chimeric receptor co-stimulated factor and a TCR chimeric receptor T cell activating domain which are connected in series. Moreover, the invention discloses an encoding gene of the anti-EGFRvIII chimeric antigen receptor, a recombinant expression vector, a construction method of the recombinant expression vector, and an application. Secretion of cell factors and an in-vitro killing effect of CAR-T cells are obviously improved, and the CAR-T cells have an outstanding clinical treatment effect.

The invention discloses an anti-CD20 chimeric antigen receptor, an encoding gene, a recombinant expression vector, a construction method of the recombinant expression vector and an application. The anti-CD20 chimeric antigen receptor comprises CD8 leader chimeric receptor signal peptide, CD20 VL, Optimal Linker C, a CD20 single-chain antibody heavy chain VH, a CD8 Hinge chimeric receptor hinge, a CD8 Transmembrane chimeric receptor transmembrane domain, a CD137 chimeric receptor co-stimulated factor and a TCR chimeric receptor T cell activating domain which are connected in series. Moreover, the invention discloses an encoding gene of the anti-CD20 chimeric antigen receptor, a recombinant expression vector, a construction method of the recombinant expression vector, and an application. Secretion of cell factors and an in-vitro killing effect of CAR-T cells are obviously improved, and the CAR-T cells have an outstanding clinical treatment effect.

The present invention discloses a malignant glioma CAR-T therapeutic vector based on OCTS technology, including lentiviral backbone plasmid, human EF1α promoter (SEQ ID NO.14), OCTS chimeric receptor domain and PDL1 single-chain antibody ; OCTS chimeric receptor domain includes: CD8 leader chimeric receptor signal peptide (SEQ ID NO.15), PDL1 single-chain antibody light chain VL (SEQ ID NO.16), PDL1 single-chain antibody heavy chain VH (SEQ ID NO.16) ID NO.17), EGFRvIII single-chain antibody light chain VL (SEQ ID NO.18), EGFRvIII single-chain antibody heavy chain VH (SEQ ID NO.19), antibody internal hinge Inner-Linker (SEQ ID NO.20), Single-chain antibody Inter-Linker (SEQ ID NO.21), CD8 Hinge chimeric receptor hinge (SEQ ID NO.22), CD8 Transmembrane chimeric receptor transmembrane region (SEQ ID NO.23), TCR chimeric receptor Synthetic receptor T cell activation domain (SEQ ID NO.26) and chimeric receptor co-stimulatory factor region. In addition, the invention also discloses the construction method of the carrier and its application in the preparation of medicine for treating malignant glioma.

Provided is an OCTS technology-based myeloid leukemia chimeric antigen receptor T-cell immunotherapy (CAR-T) therapeutic vector, which comprises: a lentiviral backbone plasmid, a human elongation factor 1 alpha (EF1α) promoter, an OCTS chimeric receptor area and a programmed death-ligand 1 (PDL1) single chain antibody; the OCTS chimeric receptor area comprises: a cluster of differentiation 8 (CD8) leader chimeric receptor signal peptide, a CD33 single-chain antibody light chain VL and heavy chain VH, a CD123 single chain antibody light chain VL and heavy chain VH, an intra-antibody hinge Inner-Linker, an inter-single chain antibody hinge Inter-Linker, a CD8 Hinge chimeric receptor hinge, a CD8 Transmembrane chimeric receptor transmembrane region, a T cell receptor (TCR) chimeric receptor T cell activation area, and a chimeric receptor co-stimulatory factor zone. Further provided are a method for constructing the vector and an application thereof in the preparation of a medicament for treating myeloid leukemia.

The invention discloses a CD22-taregted replication-defective recombinant lentivirus CAR-T transgenic vector. The vector comprises a prokaryotic replicon pUC Ori sequence for plasmid replication, an ampicillin-containing resistance gene AmpR sequence for mass amplification of a target strain, a virus replicon SV400ri sequence for enhancing replication within eukaryotic cells, a lentivirus packaging cis element for lentivirus packaging, ZsGreen1 green fluorescence protein for expression of green fluorescence of the eukaryotic cells, an IRES ribosome binding sequence for common transcriptional expression of the protein, a human EF1[alpha] promoter for eukaryotic transcription of a chimeric antigen receptor gene, a chimeric antigen receptor for constituting the second or the third generation of CAR integrating identification, transferring and promoting, and an eWPRE element for enhancing a transgenic expression efficiency. In addition, the invention also discloses a construction method and an application of the vector. The vector disclosed by the invention can significantly improve secretion of cell factors and an in vitro killing effect of CAR-T cells; and the vector is obvious in effect on the clinical treatment of precursor B-cell acute lymphocytic leukemia.