31 results about "CD155" patented technology

The present invention relates to a method of diagnosing, classifying and grading of tumor growths and to determine whether the use of chimeric polioviruses is a proper course for the treatment of the tumors. More particularly, the method is directed to the use of antibodies to a poliovirus receptor (PVR), CD155, to detect the presence of CD155 on tumor cells in various organs, such as: breast, colon, bronchial passage, epithelial lining of the gastrointestinal, upper respiratory and genito-urinary tracts, liver, prostate and the brain.

The present invention provides a newly identified B7 receptor, zB7R1 that functions as lymphocyte inhibitory receptor, which is a PD-1-like molecule and is expressed on T cells. The present invention also provides the discovery of zB7R1's ability to bind to CD155. Methods and compositions for modulating zB7R1-mediated negative signaling and interfering with the interaction of its counter-receptor for therapeutic, diagnostic and research purposes are also provided.

The present invention provides a newly identified B7 receptor, zB7R1 that functions as lymphocyte inhibitory receptor, which is a PD-1-like molecule and is expressed on T cells. The present invention also provides the discovery of zB7R1's ability to bind to CD155. Methods and compositions for modulating zB7R1-mediated negative signaling and interfering with the interaction of its counter-receptor for therapeutic, diagnostic and research purposes are also provided.

A novel and stable attenuated poliovirus, which replicates in neuroblastoma cells, is produced by engineering an indigenous replication element (cre), into the 5′ non-translated genomic region and inactivating the native cre element located in the coding region of 2C (mono-crePV). The stably attenuated poliovirus replicates in a neuroblastoma model (Neuro-2aCD155 tumors) expressing CD155, the poliovirus receptor, and is effective for oncolytic treatment and cure of solid tumors, such as neuroblastoma.

The invention provides an anti-TIGIT monoclonal antibody and application thereof. The anti-TIGIT monoclonal antibody comprises a heavy chain variable region and a light chain variable region. The heavy chain variable region comprises a heavy chain CDR1 as shown in SEQ ID NO:1, a heavy chain CDR2 as shown in SEQ ID NO:2 and a heavy chain CDR3 as shown in SEQ ID NO:3; the light chain variable region comprises a light chain CDR1 as shown in SEQ ID NO:4, a light chain CDR2 as shown in SEQ ID NO:5 and a light chain CDR3 as shown in SEQ ID NO:6. The anti-TIGIT monoclonal antibody disclosed by the invention is strong in specific recognition and binding capacity to antigen TIGIT, can effectively block the binding of the TIGIT and the ligand CD155 thereof, and is wide in application prospect.

The invention provides a recombinant fusion protein TIGIT-Fc and application in resisting transplant rejection thereof. The linear tandem polypeptide is capable of inducing specific T cell response toexert an immunoprotective effect. The amino acid sequence of the recombinant fusion protein TIGIT-Fc is shown in SEQ ID NO: 1. The nucleotide sequence for encoding the recombinant fusion protein TIGIT-Fc is shown in SEQ. ID. NO: 2. The recombinant fusion protein TIGIT-Fc can effectively regulate macrophage polarization by interfering CD226 / TIGIT-CD155 signaling pathways, which is conducive to theinduction of allograft tolerance.

The invention discloses an anti-TIGIT nanobody and application thereof, and particularly provides an anti-TIGIT nanobody and a sequence thereof. The invention also provides a coding sequence encodingthe nanobody or a VHH chain thereof, a corresponding expression vector and a host cell capable of expressing the nanobody, as well as a production method of the nanobody. The nanobody can block the interaction between TIGIT and CD155 on the surface of CT26 cells, and can effectively bind to the TIGIT protein on the cell surface; the nanobody can recognize human and macaca fascicularis TIGIT; the blocking activity of the nanobody is significantly better than a control antibody Tiragolumab; and the nanobody has a significant activating effect on T cells, and the activation effect is significantly better than that of the control antibody Tiragolumab.

The invention provides a construction method of a CD155 gene humanized non-human animal. A nucleotide sequence for encoding human CD155 protein is introduced into a non-human animal genome in a homologous recombination manner; the humanized CD155 protein can be normally expressed in the animal; and the animal can be used as an animal model for human CD155 signal mechanism research and tumour and immune disease drug screening. The important application value is realized on the research and development of new drugs of immune targets. The invention also provides humanized CD155 protein, a humanized CD155 gene, a targeting vector of the CD155 gene, a non-human animal obtained by the construction method, and application of the non-human animal in the field of biological medicines.

The invention discloses a method for efficiently knocking out a TIGIT gene in an NK cell. The method uses a CRISPR / Cas9 gene editing system to introduce a compound of sgRNA and Cas9 proteins into theamplified NK cell in an electroporation transfection manner, and the sequence of the sgRNA is any one selected from sequences shown in SEQ ID NO.1-4. By adopting the method disclosed by the invention,the knockout efficiency of the TIGIT gene in the NK cell can be close to 80%, the knockout efficiency is high, and the obtained NK cell not expressing the TIGIT can relieve the immunosuppressive effect of CD155 + tumor cells on the NK cell. Compared with wild NK cells, the obtained NK cell not expressing the TIGIT shows stronger anti-tumor activity in in-vivo and in-vitro experiments. The recognition and killing activity of the NK cell on tumor cells is obviously improved, and the NK cell is expected to be developed into a safe and effective anti-tumor biological preparation.

The invention discloses application of GnT-II gene down-regulation expression as a liver cancer prognosis marker. A CRISRP human whole genome coding gene knockout library is used for screening a coding gene GNT-II for regulating expression of an inhibitory immune checkpoint molecule CD155, and it is found that expression of GNT-II in tumor tissue of a liver cancer patient is positively correlatedwith expression of CD155; and furthermore, the expression of the GNT-II is obviously related to the prognosis of the liver cancer patient, that is, the higher the expression of the GNT-II in the earlymale liver cancer patient is, the poorer the prognosis of the patient is. Therefore, the GNT-II has a certain potential application value as a prognosis index in liver cancer.

The invention discloses an antibody or a derivative thereof. The antibody is combined with a human TIGIT antigen with high affinity and is used for antagonizing and inhibiting the combination of TIGIT and a ligand such as CD155, wherein the antibody comprises amino acid sequences of antigen complementarity determining regions (CDR-L1, CDR-L2 and CDR3-L3) of a light chain variable region of the antibody, and amino acid sequences of antigen complementarity determining regions (CDR-H1, CDR-H2 and CDR-H3) of a heavy chain variable region of the antibody. The invention also discloses a humanized preparation process of the antibody and amino acid sequences of a heavy chain variable region and a light chain variable region of the humanized antibody. The antibody or the derivative thereof can be used as a pharmaceutical composition component or can be prepared into a proper pharmaceutical preparation, and the antibody or the derivative thereof can be independently taken or combined with other drugs such as anti-PD-1 monoclonal antibody and the like or treatment means for use, and can be used for treating diseases such as tumors and the like.

The invention provides a PLGA multi-target composite nano reagent for targeting tumor neovascularization and a preparation method and application of the PLGA multi-target composite nano reagent, and relates to the technical field of biological medicines. According to the PLGA multi-target composite nano reagent for the targeting tumor neovascularization, a PLGA nano material is combined with a plurality of effective siRNA oligo expressed by PD-L1, CD47, PDGFR, EGFR and CD155 in a targeted silencing mode and is loaded with a plurality of DNA fragments having specific sequence and called Fastener Strand, and therefore the muiti-siRNAs (at) PLGA multi-target composite nano reagent is obtained. According to the PLGA multi-target composite nano reagent for the targeting tumor neovascularization, the multi-siRNAs (at) PLGA transfected genitourinary system tumor cell line is utilized to obviously inhibit the proliferation and migration capabilities of genitourinary system tumor cells, obviously enhance the killing activity of CD56 + NK cells and CD8 + T cells on the tumor cells and the release capability of inflammatory factors, and therefore the muiti-siRNAs (at) PLGA multi-target composite nano reagent can be used as a chemotherapeutic preparation for inhibiting the genitourinary system tumors.

The invention discloses application of TOX3 gene overexpression as a liver cancer prognosis marker. According to the application, a whole genome CRISPR activation library is utilized for screening, and the result shows that TOX3 can inhibit expression of a checkpoint inhibitor CD155. TCGA liver cancer RNA-seq data is further utilized for conducting immune infiltration analysis, the result shows that the expression level of TOX3 is in significant positive correlation with the infiltration frequency of NK cells in liver cancer tissue, in combination with the inhibition effect of CD155 on the NKcells, that TOX3 can activate the NK cells by inhibiting CD155 is further prompted, and therefore prognosis of a liver cancer patient is promoted. Therefore, TOX3 has certain potential application value as a prognosis index in liver cancer.

The invention discloses a method for efficiently knocking out a CD96 gene in an NK cell. The method comprises the step of introducing a compound of sgRNA and Cas9 protein into an amplified NK cell inan electroporation transfection manner by using a CRISPR / Cas9 gene editing system, wherein the sequence of sgRNA is selected from any one of sequences as shown in SEQ ID NO. 1-10. By adopting the method disclosed by the invention, the CD96 gene in the NK cell can be knocked out, the knocking-out efficiency is relatively high, and the obtained NK cell which does not express CD96 can relieve the immunosuppression effect of CD155+ tumor cells on the NK cell. Compared with a wild type NK cell, the NK cell shows relatively strong anti-tumor activity in in-vivo and in-vitro experiments, the recognition and killing activity of the NK cell on tumor cells is obviously improved, and the NK cell is expected to be developed into a safe and effective anti-tumor biological preparation.

The invention discloses an antibody or antigen binding fragment capable of being bonded with TIGIT and a use thereof. The invention relates to the field of antibodies, and discloses the antibody capable of being bonded with TIGIT and the use thereof. The antibody includes a heavy chain CDR1, a heavy chain CDR2, a heavy chain CDR3, a light chain CDR1, a light chain CDR2 and a light chain CDR3. Theantibody has the following advantages: the antibody can block the interaction between TIGIT and CD155 with high affinity; the antibody can be bonded with TIGIT with high specificity, but cannot be bonded with other members of CD28 family (such as CD28, PD-1 and CTLA4); and the antibody can activate immune cells to kill tumor cells.

The invention discloses a humanized anti-human TIGIT antibody and application thereof. The anti-human TIGIT antibody disclosed by the invention contains the heavy chain variable region VH(subscript) and the light chain variable region VL(subscript), and the VH(subscript) and the VL(subscript) are composed of the complementarity determining region and the framework region, respectively; the complementarity determining regions of the VH(subscript) and the VL(subscript) are composed of CDR1, CDR2 and CDR3, respectively; the amino acid sequences of CDR1, CDR2 and CDR3 of the VH(subscript) are shown as the amino acids at the 30-35th site, at the 50-66th site and at the 99-107th site of SEQ ID No. 10; and the amino acid sequences of CDR1, CDR2 and CDR3 of the VL(subscript) are shown as the amino acids at the 23-33rd site, at the 49-55th site and at the 88-96th site of SEQ ID No. 9. The antibody disclosed by the invention can bind to TIGIT with high affinity, can effectively block the binding of CD155 and TIGIT, and has anti-tumor activity.

The invention discloses a novel recombinant oncolytic vaccinia virus for blocking immune inspection point and activating immune co-stimulation signal channels, a construction method for the novel recombinant oncolytic vaccinia virus and application of the novel recombinant oncolytic vaccinia virus. The novel recombinant oncolytic vaccinia virus for blocking the immune inspection point and activating the immune co-stimulation signal channels can selectively replicate in tumor cells and dissolve the tumor cells and meanwhile express and secrete a soluble protein sCD155; and the soluble protein sCD155 is an extracellular region of a protein CD155 and can specifically bond acceptors TIGIT and CD226 of the protein CD155. The novel recombinant oncolytic vaccinia virus VV-sCD155 disclosed by theinvention has multiple antitumor actions of dissolving tumors, activating antitumor immunization and the like, only selectively replicates in the tumor cells, has very high safety and has a good antitumor drug development prospect.

The invention belongs to the field of biology, and relates to an anti-TIGIT antibody or an antigen-binding fragment thereof, a composition and an application thereof. The anti-TIGIT antibody and its antigen-binding fragment of the present invention can effectively block the combination of TIGIT and its ligands CD155 and CD112, thereby effectively promoting the activation of T cells, and have good anti-tumor application prospects.

The invention relates to the technical field of crude drugs and molecular biology, in particular to application of CD155 in diagnosis and treatment of cervical cancer. It is found for the first time that the expression quantity of CD155 is related to multiple molecular pathological indexes of cervical cancer, AKT / mTOR activity and an NF-kappa B pathway can be inhibited by silencing CD155, autophagy and apoptosis can be activated, and malignant progression of cervical cancer can be effectively inhibited by specifically knocking out CD155. In addition, silencing of CD155 inhibits the progress of the cell cycle by down-regulating CyclinD1 and up-regulating P27 KIP1. The discovery shows that the CD155 can be used as a molecular biomarker for diagnosing and treating cervical cancer, and can also be potentially used as a valuable treatment target for cervical cancer patients, so that the CD155 has good practical application value.

The present invention provides an anti-TIGIT monoclonal antibody and application thereof, the anti-TIGIT monoclonal antibody comprises a heavy chain variable region and a light chain variable region; the heavy chain variable region comprises SEQ ID NO:1 The heavy chain CDR1, the heavy chain CDR2 shown in SEQ ID NO:2 and the heavy chain CDR3 shown in SEQ ID NO:3; the light chain variable region includes the light chain CDR1 shown in SEQ ID NO:4, SEQ ID NO:4 Light chain CDR2 shown in ID NO:5 and light chain CDR3 shown in SEQ ID NO:6. The anti-TIGIT monoclonal antibody of the invention has strong specific recognition and binding ability to the antigen TIGIT, can effectively block the combination of TIGIT and its ligand CD155, and has broad application prospects.

The invention discloses a method for efficiently knocking out the CD96 gene in NK cells. The method uses a CRISPR / Cas9 gene editing system to introduce a complex of sgRNA and Cas9 protein into amplified NK cells by electroporation transfection wherein: the sequence of the sgRNA is selected from any one of the sequences shown in SEQ ID NO.1-10. The method of the present invention can realize the knockout of CD96 gene in NK cells, not only the knockout efficiency is high, but also the obtained NK cells that do not express CD96 can relieve the immunosuppressive effect of CD155+ tumor cells on NK cells. Wild-type NK cells show stronger anti-tumor activity in both in vivo and in vitro experiments, significantly improving the recognition and killing activities of NK cells on tumor cells, and are expected to be developed into safe and effective anti-tumor biological agents.

A reliable assay to specifically detect CD155 in tissue sections has widespread use because CD155 is expressed widely among tumor types. Additionally, detected expression of CD 155 in glioblastoma cells is at levels commensurate with susceptibility to PVSRIPO (a poliovirus construct) infection and killing. An anti-CD155 antibody can achieve mono-specific detection of CD155 in immunoblots of tumor homogenates and immunohistochemistry of tumor formalin fixed, paraffin embedded sections. The assay can be used to determine appropriate use of PVSRIPO in oncolytic immunotherapy against cancers.

A modified polio virus receptor (PVR / CD155) gene including one or more mutations in exons selected from exons 2, 3 and 4 of poliovirus receptor (PVR / CD155) gene having SEQ ID No.1. More specifically, cell lines including the modified gene and method of producing the same using clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (CRISPR-Cas9) system. The cell line is refractory (non-permissive) to poliovirus and susceptible to most Enteroviruses and many other human viruses. Further, the cell line can be applied in the fields of research, diagnostic and therapy.

The invention discloses the application of TOX3 gene overexpression as a liver cancer prognosis marker. The present invention uses genome-wide CRISPR activation library screening to find that TOX3 can inhibit the expression of checkpoint inhibitor CD155. Further analysis of immune infiltration using TCGA liver cancer RNA-seq data found that the expression level of TOX3 was significantly positively correlated with the infiltration frequency of NK cells in liver cancer tissues. Combined with the inhibitory effect of CD155 on NK cells, it was further suggested that TOX3 may activate NK cells by inhibiting CD155 , which is beneficial to the prognosis of liver cancer patients. Therefore, TOX3 has a certain potential application value as a prognostic indicator in liver cancer.

The invention discloses an effect of inhibiting tumor of CD226 extracellular domain protein. The CD226 extracellular domain protein is a protein consisting of an amino acid sequence shown by SEQ ID NO:1. The protein disclosed by the invention can be combined with CD112 and CD155, can be used for effectively closing binding sites between CD226 and target cells and inhibiting the cellular poison activity of NK cells, can be used as an inhibitor of the NK cells for treating autoimmune diseases on the one hand, and can generate an inhibitory action on proliferation of tumor cells after being combined with CD112 or CD155 molecules on the surfaces of the tumor cells on the other hand. Therefore, the protein can be used for inhibiting the proliferation of tumors in a tumor patient with a low immunologic function. Moreover, because the protein is a human body natural protein, an immunologic reaction of an organism is rarely caused. The invention relates to application of the CD226 extracellular domain protein in preparation of medicaments for inhibiting tumor cell proliferation.