188 results about "Car t cells" patented technology

The invention discloses application of kaempferol in promotion of gene editing, and belongs to the field of biological medicine. The application specifically comprises kaempferol as an accelerant for CRISPR (clustered regularly interspaced short palindromic repeats) gene editing and application of kaempferol in preparation of non-viral site-specific integrated CAR T cells. The invention finds that the kaempferol can significantly increase the CRISPR gene editing efficiency, and cell experiments find that the kaempferol has a significant promotion effect on the positive rate of CAR T cells after electrotransfection, and the tumor killing function of the T cells is greatly improved.

This document provides methods and materials involved in treating cancer. For example, methods and materials for modulating (e.g., increasing or decreasing) an interleukin-1 (IL-1) signaling pathway (e.g., an IL-1βsignaling pathway) during an adoptive cell therapy (e.g., a chimeric antigen receptor (CAR) T cell therapy) are provided. In some cases, one or more inhibitors of an interleukin-1 receptor antagonist (IL-1RA) polypeptide can be used to increasing IL-1 signaling (e.g., to reduce immunosuppression of the administered cells). In some cases, CAR T cells having a reduced level of an interleukin 1 receptor, type I (IL-1R1) polypeptide can have decreased IL-1 signaling (e.g., to reduce T cell toxicity associated with the administered cells).

The invention discloses a CAR donor plasmid, a T cell as well as a preparation method and application of the CAR donor plasmid and the T cell, and belongs to the field of genetic engineering and immune cell therapy. An RNP compound and donor plasmid DNA are transferred into a T cell through electroporation, and a CAR expression unit is integrated into a T cell genome at a fixed point to prepare the CAR T cell. The donor plasmid DNA comprises a plasmid skeleton, a homologous arm sequence, an EF1 alpha core promoter, a CAR expression element and an SV40 poly A termination signal. The number of base pairs of the plasmid is 4544 bp, the toxicity of the plasmid to T cells after electroporation can be effectively reduced, and the T cell viability and the CAR integration efficiency are improved. Compared with dsDNA and ssDNA, the plasmid DNA is convenient to prepare and low in cost; therefore, the plasmid is taken as the donor template DNA, and the CRISPR / Cas9 technology is combined, so that the use of a virus vector can be avoided to improve the safety of the CAR T cell, and the production cost of the preparation of the CAR T cell can be effectively reduced.

An oncolytic poxvirus encoding a truncated human CD19 is used in conjunction with a chimeric antigen receptor to treat solid tumors.

Provided herein are anti-idiotypic antibodies that specifically recognize anti-CD70 antibody portions, particularly anti-CD70 antibody portions present in recombinant receptors, including chimeric antigen receptors (CARs). The present disclosure further relates to the use of anti-idiotypic antibodies to specifically identify and / or select cells expressing such recombinant receptors, such as anti-CD70 CAR T cells. The present disclosure further relates to the use of anti-idiotypic antibodies to specifically activate such cells.

The present disclosure relates to mesothelin chimeric antigen receptors (CARs), T cell engaging molecules (TEAMs), anti-mesothelin-CAR T cells optionally comprising TEAMs, and methods of use thereof.

The present invention discloses a modified chimeric antigen receptor T cell, its preparation method, and its use. The present invention prepares cells, such as chimeric antigen receptor T cells, modified with a hydrophobic two-dimensional sheet material. Compared to simple chimeric antigen receptor T cells, these cells can bind to more leukemia cells, enhancing their recognition and killing abilities. Furthermore, the nanomaterial's high specific surface area provides space for drug loading, enabling the combination of CAR T cells with other therapies.

The application discloses an application of kaempferol in promoting gene editing and belongs to the field of biological medicines. The application specifically comprises kaempferol as a promoter of CRISPR gene editing and the application of kaempferol in preparing non-virus site-specific integration CAR T cells. It is found that kaempferol can significantly increase the efficiency of CRISPR gene editing, and it is found through cell experiments that kaempferol has a significant promoting effect on the positive rate of CAR T cells after electrotransformation, and greatly improves the tumor killing function of T cells.

Systems and methods are disclosed for predicting whether a patient-specific CAR T drug product for a target patient would undergo growth termination. An example method includes: receiving quantitative data for a set of growth termination parameters; generating an input feature vector comprising the quantitative data for the set of growth termination parameters; and applying, into a trained machine learning model, the input feature vector to generate an output feature vector predicting whether the patient-specific CAR T drug product would undergo growth termination.

The present disclosure relates generally to methods of making a population of trispecific CAR-expressing immune cells that provide several improvements over existing manufacturing methods, thereby enabling production of a robust supply of clinically useful CAR T-cell therapies.

The invention discloses application of amifostine to improvement of fixed-point insertion efficiency of a genome, and belongs to the field of biological medicine. Specifically, amifostine provided by the invention can significantly improve the CRISPR gene editing efficiency, and especially can be used for preparing non-viral site-specific integrated CAR T cells. Through cell experiments, it is found that amifostine has a remarkable promoting effect on the positive rate of CAR T cells after electrotransfection, and the tumor killing function of the T cells is greatly improved.

The invention relates to a CLD18A2-targeted T lymphocyte as well as a preparation method and application thereof. The inventor successfully finds a target gene CLD18A2 suitable for developing CAR T cells from a plurality of tumor related genes for the first time, and successfully prepares CLD18A2-targeted CAR T cells, so that a brand new treatment means is provided for pancreatic cancer, gastric cancer and other tumors.

The present disclosure relates to methods and compositions for the treatment of a mammalian subject suffering from lupus the method comprising, administering to said subject a therapeutically effective amount of an orthogonal CAR-T cell directed against a B-cell antigen in combination with an engineered orthogonal IL2 ligand that selectively activates orthogonal CAR T cell expressing an engineered orthogonal CD122 receptor. In some embodiments, the lupus is systemic lupus erythramatosis (SLE). In some embodiments, the lupus is lupus nephritis. In some embodiments the subject suffering from lupus is also suffering from cytopenia. In some embodiments the methods are practiced in the absence of prior lymphodepletion of the subject.

Chimeric antigen receptor (CAR) linking molecules and protein entities and dimers comprising an extracellular domain of an antigen present on a cancer cell and a first immune cell effector domain are disclosed, as well as their use in co-treatment of cancer with CAR immune cells.

The disclosure provides constructs that permit hypoxia-controlled expression to be selectively active in tumors and tumor microenvironments, thereby reducing off target effects of expressed therapeutic genes, such as CAR T cells.

CD38 is also expressed in a variety of hematological malignancies, including multiple myeloma. In the present invention, the inventors obtained a new antibody against CD38 that can be used to produce bispecific antibodies and CAR T cell populations. In particular, the inventors reported the development of Bi38-3, a new bispecific T cell engager that targets CD38 on MM cells and forms cytotoxic T cells through CD3ε. Bi38-3 lacks the Fc region of natural mAbs, which contributes to the resistance process, but triggers T cell proliferation, cytokine release, and lysis of CD38-positive MM cells in vitro. Similarly, Bi38-3 induces autologous T cells to eliminate tumor plasma cells isolated from MM patients at diagnosis and relapse. The cytotoxicity triggered by Bi38-3 is limited to cells expressing high levels of CD38 and maintains the integrity of T, B, and NK lymphocytes in vitro. Importantly, Bi38-3 rapidly reduced tumor cells in the MM1.S xenograft mouse model of human MM. In summary, the results show that the antibody of the present invention is an effective agent for specifically eliminating CD38-positive malignant cells without significantly affecting CD38-low-expressing cells, and is a promising new immunotherapy tool for treating malignant blood diseases, especially multiple myeloma.

The invention provides a polymer lipid hybrid nanoparticle with T cell activation ability, which is characterized in that the polymer lipid hybrid nanoparticle comprises a cationic polymer, an auxiliary lipid, cholesterol and a polyethylene glycol derived lipid, and the cationic polymer comprises a copolymer prepared from polyethyleneimine and p-toluenesulfonyl arginine. The polymer lipid hybrid nanoparticles provided by the invention have dual capabilities of T cell activation and transfection, can realize one-step activation and transfection of primary T cells, greatly shortens the preparation period, and reduces the preparation complexity. Besides, CAR-T cells generated by delivering CAR mRNA through the polymer lipid hybrid nanoparticles RT LNP have excellent cell killing ability in vitro, and can specifically secrete killer cytokines, so that specific and efficient killing of target cells is realized, and the CAR-T cells have good application prospects. It is verified that the polymer lipid hybrid nanoparticles developed in the invention are a promising platform for rapid production of mRNA CAR T cell products.

To provide cells containing anti-CD33 chimeric antigen receptors (CARs); anti-CLL1 CARs; and anti-CD123 and / or anti-CAR FLT3 CARs. [Solution] The aforementioned cells can be used in the treatment of diseases such as acute myeloid leukemia (AML). In a first aspect, the present invention provides CAR-expressing cells that target multiple antigens associated with acute myeloid leukemia (AML). These cells target three or four of the following antigens: CD33, CLL-1, CD123, and FLT3. For example, the cells may include anti-CD33 chimeric antigen receptor (CAR); anti-CLL1 CAR; and anti-CD123 CAR.

Disclosed herein is a method of providing an anti-cancer immunity in a subject with a bone metastatic cancer. The method involves co-administering to the subject an effective amount of a gamma-delta T cell stimulating agent and an effective amount of a γδ CAR T cell that binds a tumor antigen. Also disclosed herein is a recombinant T cell that expresses a gamma-delta T cell receptor (TCR) and a chimeric antigen receptor (CAR) polypeptide.

Disclosed herein is a small molecule targeted drug conjugate for anti-influenza chemotherapy and immunotherapy. The disclosed drug conjugate may form an adaptor to recruit additional CAR T cells or other immune cells for precise elimination of influenza virus-infected cells in a subject. Concurrently administered antibodies or pre-existing immunity in influenza-virus infected subject works well with the targeted conjugate to eliminate virus infected cells, saving valuable time for rescuing late stage patients.

The application discloses application of amifostine in improving genome site-directed insertion efficiency and belongs to the field of biological medicines. Specifically, the application proposes that amifostine can significantly increase the efficiency of CRISPR gene editing, and can be used for preparing non-viral site-directed integration CAR T cells. It is found through cell experiments that amifostine has a significant promoting effect on the positive rate of CAR T cells after electrotransformation, and greatly improves the tumor killing function of T cells.

Disclosed herein are engineered polyfunctional CD4+ T cells / CAR T cells and methods of their use for the treatment of cancers. One embodiment provides a method of producing polyfunctional CD4+ T cells by constitutively activating STAT5A in the cells to induce a polyfunctional phenotype. Also provided is a method of reversing exhaustion in tumor-specific CD4+ T cells by engineering the cells to express Fos, Jun, Nr4a1, or combinations thereof but not express Tox, Pdcd1, Ctla4, Haver2, Lag3, Tigit, Slam6, Nrf4a2, and administering the engineered cells to a subject.

Disclosed herein is a platform capable of generating varying concentrations of antigens in cells. Also disclosed herein are methods for screening chimeric antigen receptors (CARs), including multitarget CARs (e.g. bi-specific, tri-specific), and CAR T cells capable of distinguishing between two cells with varying levels of the same antigen, using a highthroughput in vitro and / or in vivo approach with single domain antibodies. These methods offer a rapid way to obtain functional CAR T-cells and other modified immune cells to be used in, for example, the treatment of cancer. In some embodiments, the method / use is part of an immunotherapy treatment.

This invention relates to recombinant mammalian cells and their use in treating cancer. The present invention specifically relates to the co-expression of an adapter CAR and a conventional CAR in CAR T cells and the use of these cells in treating lymphoma. The invention also relates to pharmaceutical compositions comprising such recombinant mammalian cells, as well as their uses in cancer therapy.

In some aspects, the present disclosure provides methods for generating CAR T cells in situ. The present disclosure provides lipid nanoparticles that selectively target a spleen cell, in particular, a lymphocyte such as a T cell. The lipid nanoparticle provided herein contain a five component composition that includes a permanently anionic lipid giving the lipid nanoparticle an apparent pKa of less than 6.

The present disclosure relates to DNA constructs encoding a CD19-specific chimeric antigen receptor (CAR) and other recombinant proteins, for example, a CD70-binding protein or a CD70-specific CAR, and engineered immune cells (e.g., CD19-specific CAR T cells or CD19 / CD70 dual CAR T cells) comprising the DNA constructs, methods of making the same, and uses thereof in therapeutic applications.

Small molecule targeted drug conjugates for anti-influenza chemotherapy and immunotherapy are disclosed herein. The disclosed drug conjugates can form linkers to recruit additional CAR T cells or other immune cells for precise elimination of influenza virus-infected cells in a subject. In a subject infected with influenza virus, the co-administered antibody or pre-existing immunity functions well together with the targeted conjugate to eliminate virus-infected cells, saving valuable time for rescuing patients in advanced stages.

The present disclosure provides a method for rapid production of genetically modified immune effector cells, such as T cells, from a mixed mononuclear cell population. The method includes activating a T cell population contained in the mixed mononuclear cell population, and, following a post-activation period of up to three hours, exposing the mixed mononuclear cells containing the activated T cell population to at least one viral vector employed to transduce at least the T cell population contained in the mixed mononuclear cell population with an exogenous nucleotide. The method allows for rapid production of genetically modified immune effector cells, such as CAR T cells.

The disclosure is directed, in part, to novel drug-responsive T cell factors providing temporal and / or spatial control over T cell (e.g., CAR T cell) activation and / or proliferation, T cells comprising the T cell factors, nucleic acid encoding the T cell factors, and methods for using and producing the same.