154 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).

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.

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 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.

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.

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 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.

Methods and compositions relate to managing chimeric antigen receptor T (CAR T) cell therapy-associated diarrhea in human subjects undergoing such therapy for colorectal cancer (CRC) are disclosed. The CAR T cells target a CRC-associated antigen, such as Guanylate Cyclase C (GCC) or Carcinoembryonic Antigen (CEA). The methods comprise administering a prophylactic regimen to the subject post-infusion of CAR T cells. This regimen includes agents such as vedolizumab, infliximab, or prophylactic budesonide. Subjects are monitored for diarrhea development and severity based on predefined clinical criteria, including stool frequency or stool volume. The methods may further involve a tiered therapeutic algorithm for treating occurring diarrhea, potentially utilizing corticosteroids or antithymocyte globulin (ATG). These approaches aim to reduce the incidence, duration, and severity of CAR T induced diarrhea, thereby improving patient safety and treatment tolerability.

Disclosed are compositions and methods for targeted treatment of cancer, such as hematologic cancer. In particular, chimeric antigen receptor (CAR) T cells are disclosed that can be used with adoptive cell transfer to target and kill cancer cells with reduced antigen escape. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with hematologic cancer that involves adoptive transfer of the disclosed CAR T cells.

Disclosed are novel weak affinity IL-2 variants and uses thereof, including adoptive cell therapies by enhancing the efficacy and duration of CAR-immune cells in the treatment of cancer.

Provided are anti-idiotype antibodies that specifically recognize anti-GPRC5D antibody moieties, in particular, anti-GPRC5D antibody moieties present in recombinant receptors, including chimeric antigen receptors (CARs). The disclosure further relates to uses of antiidiotype antibodies for specifically identifying and / or selecting cells expressing such recombinant receptors, such as anti-GPRC5D CAR T cells. The disclosure further relates to uses of anti-idiotype antibodies for specifically activating such cells.

The present disclosure provides modified immune cells or precursors thereof (e.g. modified T cells) comprising a chimeric cell surface sialidase or a variant sialidase precursor protein. Compositions and methods of treatment are also provided.

The present invention relates to modified T cells and methods of making and using the same. Specifically, disclosed herein are modified primary human T cells, and populations thereof, comprising a genome in which the CTLA4, PD1, TCRA, TCRB, and / or B2M genes have been edited to produce off-the-shelf universal CAR T cells from allogeneic healthy donors, the off-the-shelf universal CAR T cells can be administered to any patient while reducing or eliminating the risk of immunological rejection or graft versus host disease, and are not susceptible to T cell inhibition; and methods for allogeneic administration of the cells to reduce the likelihood that the cells will trigger a host immune response when the cells are administered to a subject in need thereof.

Some embodiments of the methods and compositions provided herein relate to the use of hapten labeled cells to stimulate chimeric antigen receptor (CAR) T cells. In some embodiments, CAR T cells can include a CAR that specifically binds to a hapten. Some embodiments relate to the in vivo or in vitro stimulation CAR T cells by hapten labeled cells.

The invention relates to application of a CD2 / 5 / 7 knockout anti-CD2 / 5 / 7 chimeric antigen receptor T cell to T cell lymphoma and leukemia. The present invention includes compositions and methods for treating T cell lymphoma and leukemia. In certain aspects, the compositions and methods include CAR T cells that target CD2, CD5, or CD7 and modified cells in which CD2, CD5, or CD7 has been knocked out.

Provided herein are antibodies and antibody fragments that bind CA9 or ENPP3. Also provided are methods of treating clear cell renal cell carcinoma with an antibody or antibody fragment that binds CA9 and an antibody or antibody fragment that binds ENPP3.