9 results about "Receptor signaling" patented technology

The application discloses an IGF2BP2-m6A-VCAN-TLR2 signal axis in the preparation of a drug for treating intrahepatic cholangiocarcinoma lymphatic metastasis. In view of the problems of unknown intrahepatic cholangiocarcinoma lymphatic metastasis mechanism and lack of effective target, the application finds and verifies a new pathway that from insulin-like growth factor 2 mRNA binding protein 2, m6A modification regulates the expression of multi-functional proteoglycan, and then activates Toll-like receptor 2 signal, promotes macrophage secretion of vascular endothelial growth factor C and drives lymphatic metastasis. Based on this, the application provides an inhibitor targeting the signal axis, in particular, a small molecule compound 8010-8498. Experiments show that the compound can significantly inhibit cholangiocarcinoma cell migration, invasion and epithelial mesenchymal transition, reduce macrophage secretion of vascular endothelial growth factor C, and effectively inhibit tumor growth and lymphatic metastasis in a naked mouse popliteal lymph node metastasis model and a spontaneous cholangiocarcinoma model. The compound presents a synergistic effect in combination with gemcitabine and cisplatin.

The application relates to immunoconjugates for use in a method of treating bladder cancer in a human patient, wherein the method comprises administering the immunoconjugate to the patient, wherein the immunoconjugate comprises: (i) an antibody that binds to PD-1; and (ii) a mutant IL-2 polypeptide comprising the amino acid substitutions F42A, Y45A and L72G. The immunoconjugates are capable of binding in cis to PD-1 and stimulating IL-2 signalling on the same cell, providing selective IL-2 receptor signalling on PD-1 positive T cells relative to the PD-1 negative T cells. The application also relates to the use of the immunoconjugates in combination with immunotherapeutic agent, which is bacterial strain or an oncolytic virus, such as the BCG vaccine.

Disclosed herein are chimeric antigen receptor (CAR) polypeptides that can be used with adoptive cell transfer to target and kill cancers. As with other CARs, the disclosed CAR polypeptides contain an ectodomain that contains a binding domain, a hinge domain, a transmembrane (TM) domain, and an endodomain that contains a signaling region. Unlike other CARs, however, the endodomain of the disclosed CAR polypeptides contains an intracellular domain of an NK cell receptor and does not require the signaling domain from CD3 zeta (CD3ζ). Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a tumor associated antigen-expressing cancer that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

Disclosed herein are compositions and methods for modulating cell surface receptor signaling by specifically recruiting membrane phosphatases to a proximity of receptors of interest. This novel methodology, termed Receptor Inhibition by Phosphatase Recruitment (RIPR), represents a new approach to reducing and suppressing signal by receptors that signal through phosphorylation mechanisms. More particularly, the disclosure provides novel multivalent protein-binding molecules that specifically bind a cell surface receptor and antagonize the receptor signaling through recruitment of a phosphatase activity. Also provided are compositions and methods useful for producing such molecules, as well as methods for the treatment of diseases associated with the inhibition of signal transduction mediated by cell surface receptor.

This invention discloses a structured subunit vaccine based on framework nucleic acids, its preparation method, and its applications. The structured subunit vaccine comprises: framework nucleic acid, antigen, and adjuvant, wherein the antigen and adjuvant are coupled to the framework nucleic acid; the distance between the antigen and adjuvant is 5-400 nm. This structured subunit vaccine, by precisely controlling the spatial spacing between the antigen molecule and the TLR-like adjuvant at the nanoscale based on framework nucleic acid, achieves synergistic amplification of the B-cell antigen receptor and Toll-like receptor signal axes, thereby significantly improving the humoral immunogenicity of the subunit vaccine. Furthermore, the framework nucleic acid can be modified in topology and size as needed to construct multivalent, composite, and tandem structured vaccine systems, which is beneficial for wide application in various scenarios, including SARS-CoV-2, influenza, and tumor vaccines.

GUCY2C T cell antigen coupler (TAC) polypeptides having (i) an antigen-binding domain that binds GUCY2C, (ii) an antigen-binding domain that binds a protein associated with a TCR complex, and (iii) a T cell receptor signaling domain polypeptide are provided.

GUCY2C T cell antigen coupler (TAC) polypeptides having (i) an antigen-binding domain that binds GUCY2C (e.g., a nanobody), (ii) an antigen-binding domain that binds a protein associated with a TCR complex, and (iii) a T cell receptor signaling domain polypeptide are provided.

The invention relates to particular substituted deuterated heterocycle fused gamma-carbolines, their prodrugs, in free, solid, pharmaceutically acceptable salt and / or substantially pure form as described herein, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving 5-HT2A receptor, serotonin transporter (SERT) and / or pathways involving dopamine D1 / D2 receptor signaling systems, and / or the treatment of residual symptoms.