30 results about "CD155" patented technology

The present disclosure provides antibodies that specifically bind to TIGIT. The antibodies have the capacity for substantial activation of T cells and natural killer cells by inhibiting binding of TIGIT to CD155. The antibodies can be used for treatment of cancer and infectious disease, among other applications.

Provided in the present invention are an anti-CD155 antibody and the use thereof. Moreover, an obtained anti-CD155 chimeric antibody, a humanized anti-CD155 antibody, and a humanized affinity-matured anti-CD155 antibody can only specifically target and bind to a CD155 receptor and block the binding of CD155 to receptors TIGIT, CD96, and CD226 thereof, but also have the characteristic of not inducing the apoptosis of CD155 cells.

The present disclosure provides binding proteins, such as antibodies and antigen-binding fragments, which specifically bind to human CD96 receptor protein (hu-CD96) and are capable of decreasing, inhibiting, and / or fully-blocking immune regulatory effects mediated by hu-CD96. The present disclosure also provides methods of using the antibodies (and compositions thereof) to treat diseases and conditions responsive to decreasing, inhibiting and / or blocking immune regulatory function or activity mediated by CD96 binding to CD155, including effects arising from CD96 interactions with CD226 and / or TIGIT.

The present invention provides antibody drug conjugates (ADCs) of humanized anti-PVR (CD155) and use thereof in treating diseases, in particular cancer.

The present invention relates to the technical field of immune engineering, and in particular to a CD155-targeting antibody or antigen-binding fragment and a use thereof. The antibody comprises a heavy chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 23 and a light chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 24, or a heavy chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 25 and a light chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 26. The antibody has an excellent binding capability with CD155, and CAR-T cells constructed on the basis of the antibody have a significant killing capability against tumor cells expressing CD155, as well as an obvious cellular internalization effect, the capability of promoting the cytotoxic effect of NK cells, and the capability of promoting the phagocytosis effect of macrophages, thereby exhibiting an excellent anti-tumor effect.

The application provides an immune cell preparation method capable of reversing tumor microenvironment immunosuppression signals and application thereof. The method for reversing the inhibitory signals is to replace the intracellular segment of a TIGIT receptor with a 4-1BB costimulatory domain and an IL-18R and a CD3 intracellular segment, and the immune cells expressing the chimeric antigen receptor recognize CD155 in a tumor microenvironment through TIGIT, avoid loss of function or exhaustion of the immune cells, and stimulate the immune cells to exert stronger tumor killing activity.

The present invention provides anti-CD155 antibodies and their applications, and provides anti-CD155 chimeric antibodies, humanized antibodies, and affinity-matured humanized antibodies, which specifically target and bind to the CD155 receptor, inhibit the binding of CD155 to its receptors TIGIT, CD96, and CD226, and have the characteristic of not inducing apoptosis of CD155 cells.

The present invention aims to solve the problem of providing a novel combination therapy with excellent antitumor effects. The present invention provides an antitumor agent (excluding pembrolizumab as an active ingredient) which includes as an active ingredient, fobamintib or a pharmaceutically acceptable salt thereof, to be administered in combination with an immune checkpoint inhibitor (excluding a CD155 / TIGIT pathway antagonist) and at least one or more other antitumor agents to a cancer patient.

This invention belongs to the field of biomedical technology, specifically disclosing a nanomicelle FluDox-MIC, its preparation method, and its uses. This nanomicelle is formed by the self-assembly of flumatinib and doxorubicin co-loaded in mPEG-DSPE, exhibiting pH-responsive release properties. Upon entering the tumor microenvironment, it releases the drug. The released flumatinib induces the degradation of the poliovirus receptor (PVR / CD155), relieving its inhibitory signal on NK cells and reactivating innate immune surveillance. Simultaneously, low-dose doxorubicin induces significant immunogenic cell death (ICD), initiating and amplifying tumor-specific T cell-mediated adaptive immunity. Through the synergistic activation of innate and adaptive immunity, the nanomicelle of this invention can effectively inhibit melanoma growth and overcome immunotherapy resistance, showing promising clinical application prospects.

The invention provides a polypeptide, a novel multi-target chimeric antigen receptor and application of the novel multi-target chimeric antigen receptor. The polypeptide comprises a TIGIT extracellular domain polypeptide and a PD1 extracellular domain polypeptide, and the TIGIT extracellular domain polypeptide has one or more mutations compared with a TIGIT reference sequence; the PD1 extracellular domain polypeptide has one or more mutations compared with a PD1 reference sequence; the TIGIT reference sequence is an amino acid sequence as shown in SEQ ID NO: 9; the PD1 reference sequence is an amino acid sequence as shown in SEQ ID NO: 13. Therefore, the polypeptide disclosed by the invention has excellent affinity to CD155 and also shows excellent affinity to PD-L1 at the same time, and collaborative recognition of multiple targets such as PD-L1 and CD155 can be realized.

The invention provides an NK cell in-vitro efficient culture system and application, the culture system comprises a K562 engineering cell, and six proteins of IL21, IL12, IL15, CD40L, CD155 and CD112 are expressed on a cell membrane of the K562 engineering cell in a transmembrane mode; the NK cell culture composition comprises the following components: a liquid serum-free cell culture medium, 1-5% (v / v) of autologous plasma, 100-250 [mu] g / ml of an astragalus extract and 200-500 [mu] g / ml of an angelica sinensis extract, and the dosage ratio of the astragalus extract to the angelica sinensis extract is 1: 2. The NK cell with high amplification multiple, high purity and high lethality can be obtained by a culture system established by taking the K562 engineering cell constructed by the invention as a trophoblast cell, taking an astragalus extract and an angelica sinensis extract as culture additives and taking PBMC as an original culture material, and the culture system has important significance for treating cancers by cell drugs.

The application provides a bispecific antibody and application thereof, and the antibody is a double-chain antibody, which comprises a first peptide chain and a second peptide chain, wherein the first peptide chain comprises a CD3 single-chain antibody and a first Fc region, and the CD3 single-chain antibody comprises a heavy chain variable region and a light chain variable region; the second peptide chain comprises a TIGIT extracellular region and a second Fc region; the C terminal of the CD3 single-chain antibody is connected with the N terminal of the first Fc region; and the C terminal of the TIGIT extracellular region is connected with the N terminal of the second Fc region. The prepared bispecific antibody can simultaneously target CD3 and CD155, thereby mediating the killing of tumor cells by T cells, and has strong tumor inhibition capacity.

The present application relates to a kind of monoclonal antibody that can identify human CD155 antigen, its preparation method and its use in immunodetection.The present application provides a kind of anti-CD155 protein rabbit monoclonal antibody, the amino acid sequence of the heavy chain variable region of the monoclonal antibody is the amino acid sequence shown in SEQ ID NO.1;The amino acid sequence of the light chain variable region of the monoclonal antibody is the amino acid sequence shown in SEQ ID NO.2.The antibody has high specificity, sensitivity, and can specifically recognize the cell expressing CD155 protein, is suitable for immunological detection, especially immunohistochemical detection.

The invention belongs to the field of immunology, and relates to a CD155 antibody or an antigen binding fragment thereof and application thereof. The CD155 antibody or the antigen binding fragment thereof is composed of heavy chains, and the heavy chains comprise a heavy chain CDR1 as shown in any one of SEQ ID NO: 24 to SEQ ID NO: 28, a heavy chain CDR2 as shown in SEQ ID NO: 29 and a heavy chain CDR3 as shown in any one of SEQ ID NO: 30 to SEQ ID NO: 31. Compared with the prior art, the invention has the beneficial effects that the antibody or the antigen binding fragment thereof specifically aiming at CD155 is screened by using a biological genetic engineering technology, and the affinity of the antibody is better.

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 CD155-targeted antigen-binding protein and the use thereof. The present application specifically relates to an isolated antigen-binding protein capable of binding to CD155, the antigen-binding protein comprising at least one CDR in a heavy chain variable region of an antibody. Provided are a chimeric antigen receptor comprising the antigen-binding protein, an immunoconjugate, a pharmaceutical composition, a pharmaceutical combination, a nucleic acid encoding the antigen-binding protein, a vector comprising the nucleic acid molecule, a cell comprising the vector, and the use of the antigen-binding protein in the prevention and / or treatment of diseases.

The application provides an antibody or an antigen binding fragment thereof and application thereof. The antibody or the antigen binding fragment thereof comprises a heavy chain variable region CDR1, CDR2 and CDR3 sequence as shown in SEQ ID NO: 1, 2 and 3 or an amino acid sequence with at least 80% identity with SEQ ID NO: 1, 2 and 3; and a light chain variable region CDR1, CDR2 and CDR3 sequence as shown in SEQ ID NO: 4, 5 and 6 or an amino acid sequence with at least 80% identity with SEQ ID NO: 4, 5 and 6. The antibody or the antigen binding fragment thereof can bind to TIGIT, block the binding of TIGIT to a ligand CD155, release TIGIT-mediated immunosuppression, activate an immune cell anti-cancer mechanism, and then inhibit the growth and proliferation of tumors.

The present application provides a polypeptide, a novel multi-target chimeric antigen receptor and application thereof. The polypeptide comprises a TIGIT extracellular region polypeptide and a PD1 extracellular region polypeptide, wherein the TIGIT extracellular region polypeptide has one or more mutations compared with a TIGIT reference sequence; the PD1 extracellular region polypeptide has one or more mutations compared with a PD1 reference sequence; the TIGIT reference sequence is an amino acid sequence as shown in SEQ ID NO: 9; and the PD1 reference sequence is an amino acid sequence as shown in SEQ ID NO: 13. Thus, the polypeptide of the present application has excellent affinity to CD155, and also exhibits excellent affinity to PD-L1, and can realize the synergistic recognition of multi-targets such as PD-L1 and CD155.

We provide antibody-based therapeutics against CD155 that can treat CNS cancers and systemic cancers. [Solution] Humanized antibodies or antigen-binding fragments specific to the poliovirus receptor (PVR) are used to prepare antibody-drug conjugates (ADCs) that target nucleic acids, peptides, proteins, drugs, and radiopharmaceuticals to cancer cells. These antibodies can be used for checkpoint blockade, blocking PVR (CD155) from binding to TIGIT. Humanized antibodies are used either alone or in combination with other checkpoint inhibitors known in the art. Humanized antibodies modulate the PVR-DNAM-1 axis to upregulate DNAM1 (CD226) expression on T cells or NK cells, thereby restoring the immune surveillance mechanism. The antibodies are incorporated into CAR-T cells or CAR NK cells.

To provide antibodies to TIGIT.SOLUTION: The present disclosure provides antibodies that specifically bind to TIGIT. The antibodies have the capacity for substantial activation of T cells and natural killer cells by inhibiting binding of TIGIT to CD155. The antibodies can be used for treatment of cancer and infectious disease, among other applications. Provided herein are, in particular, antibodies that specifically bind to TIGIT, and, among other applications, their use for treatment of cancer and infectious disease.SELECTED DRAWING: None

The present application provides: an anti-CD155 antibody or an antigen-binding fragment thereof; a conjugate of the antibody or antigen-binding fragment thereof and a drug; a composition for detecting CD155, a composition for diagnosing cancer, and a pharmaceutical composition for preventing, ameliorating, or treating cancer, each comprising the antibody or antigen-binding fragment thereof; and a pharmaceutical composition for preventing, ameliorating, or treating cancer comprising the conjugate, and thus achieves a better anticancer effect.

The present invention belongs to the field of immunoengineering technology, and specifically relates to an antibody or antigen-binding fragment targeting CD155 and its application. The antibody includes a heavy chain variable region having at least 70% identity with the sequence shown in SEQ ID NO: 23 and a light chain variable region having at least 70% identity with the sequence shown in SEQ ID NO: 24, or a heavy chain variable region having at least 70% identity with the sequence shown in SEQ ID NO: 25 and a light chain variable region having at least 70% identity with the sequence shown in SEQ ID NO: 26. The antibody has excellent binding ability to CD155, and the CAR-T constructed based on the antibody has significant killing ability against tumor cells expressing CD155, as well as obvious cell internalization, promotion of NK cell killing toxicity and promotion of macrophage phagocytosis, showing excellent anti-tumor effect.

The invention belongs to the field of immunology, and relates to a CD155 binding molecule and application thereof. The CD155 binding molecule is composed of heavy chains, and the heavy chains comprise a heavy chain CDR1 as shown in any one of SEQ ID NO: 23 to SEQ ID NO: 26, a heavy chain CDR2 as shown in SEQ ID NO: 27 and a heavy chain CDR3 as shown in any one of SEQ ID NO: 28 to SEQ ID NO: 31. Compared with the prior art, the invention has the beneficial effects that the specific single-domain antibody aiming at CD155 is screened by using a biological genetic engineering technology, and the affinity of the antibody is better.

To provide a novel combination therapy that exhibits excellent antitumor effects. [Solution] An antitumor agent containing futivatinib or a salt thereof as the active ingredient (not containing pembrolizumab as the active ingredient) administered in combination to cancer patients with an immune checkpoint inhibitor (excluding CD155 / TIGIT pathway antagonists) and at least one other antitumor agent.

The invention relates to the technical field of biology, in particular to a method for detecting biological functions of mesenchymal stem cells. The invention provides a method for evaluating the functions of mesenchymal stem cells by using the combination of surface molecules CD155 and secretory factors IDO, which is different from the conventional detection method and is characterized in that the biological functions of the cells are rapidly judged by detecting the surface CD155 of the mesenchymal stem cells through flow cytometry and detecting the concentration of cytokines IDO through an ELISA (Enzyme-Linked Immuno Sorbent Assay) method. The biological functions refer to proliferation, differentiation, adhesion, anti-apoptosis, factor secretion and anti-inflammatory functions of the mesenchymal stem cells, and the method is rapid and accurate, has a wide application prospect and is worthy of popularization and application.

The present application provides an anti-CD155 antibody or an antigen-binding fragment thereof; a composition for detecting CD155, a composition for diagnosing cancer, and a pharmaceutical composition for preventing, ameliorating, or treating cancer, each comprising the antibody or antigen-binding fragment thereof; and a conjugate of the antibody or antigen-binding fragment thereof and a drug, and uses thereof for treating cancer, thereby achieving superior anticancer effects.

The invention provides a bispecific antibody targeting PVRIG and TIGIT and an application of the bispecific antibody. The bispecific antibody comprises a first antigen binding region and a second antigen binding region, wherein the first antigen binding region has PVRIG molecular binding activity; and a second antigen binding region, wherein the second antigen binding region has TIGIT molecule binding activity; wherein the first antigen binding region is connected with the second antigen binding region. The bispecific antibody prepared by the invention can be combined with human PVRIG and TIGIT proteins with high affinity, and can effectively block the combination of PVRIG and CD112 and the combination of TIGIT and CD155, thereby promoting the killing of human PBMC on tumor cells and enhancing the cytokine secretion function of CD8T cells.

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.

A humanized antibody or antigen binding fragment specific for the poliovirus receptor (PVR) is used to prepare antibody drug conjugates (ADCs) to target nucleic acids, peptides, proteins, drugs and radiopharmaceuticals to cancer cells. These antibodies can be used for checkpoint blockade where binding to PVR (CD 155) blocks PVR from binding TIGIT. The humanized antibodies are used either alone or in combination with other checkpoint inhibitors known in the art. The humanized antibody modulates the PVR-DNAM-1 axis to upregulate DNAM1 (CD 226) expression on T cells or NK cells, thereby restoring immunosurveilance mechanisms. The antibody is incorporated in CAR-T cells or CAR NK cells. Bispecific antibodies are produced by incorporating the anti-CD 155 antibodies or antigen binding fragments to engage T cells or NK cells to fight cancers expressing CD155. The anti-CD 155 antibodies bind to Nectin 4 thus enabling targeting cancers that express Nectin 4.