30 results about "CD155" patented technology

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 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 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 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 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 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.

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.