83 results about "Car t cells" patented technology

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 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 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.

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.

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.

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.

The present disclosure provides methods of treating a subject having or suspected of having a B cell malignancy or a B cell mediated disorder by administering hypoimmune allogenic CD19-directed CAR T cells. Also disclosed are pharmaceutical compositions comprising hypoimmune allogenic CD19-directed CAR T cells, for use in treating a subject having or suspected of having a B cell malignancy or a B cell mediated disorder.

The present invention provides compositions and methods for treating cancer in a patient. In one embodiment, the method comprises a first-line therapy comprising administering to a patient in need thereof a genetically modified T cell expressing a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain and monitoring the levels of cytokines in the patient post T cell infusion to determine the type of second-line of therapy appropriate for treating the patient as a consequence of the presence of the CAR T cell in the patient.

Provided herein are CD70-binding proteins comprising a CD70-binding domain and a transmembrane domain, engineered immune cells comprising the CD70-binding proteins, and methods of making and using the same. Also provided herein are engineered immune cells e.g. CAR (chimeric antigen receptor) T cells for administration to patients to treat cancer (e.g., solid tumors and hematologic tumors) and other unwanted conditions. The cells are engineered to functionally express a first antigen binding molecule e.g. a CD70 CAR and a second antigen binding molecule e.g. a second CAR that binds a target molecule characteristic of the cancer or other disease or unwanted condition. The cells may be further engineered to reduce the functional expression level of one or more of TRAC, CD52 and CD70. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering them.

This specification provides methods for detecting the expression of bicistronically expressed polypeptides, for example, in a population of immune cells, such as a population of CAR T cells, that have been manipulated into chimeric cytokine receptors. In one aspect, this disclosure provides an in vitro method for detecting bicistronically expressed polypeptides in chimeric antigen receptor (CAR) T cells.

The disclosure describes antibodies chimeric antigen receptors (CARs), CAR T cell therapeutics, and their use in treating solid cancers. In particular, the disclosure describes antibodies and CAR T constructs that bind to NRCAM in variety of solid tumors.

Provided herein are second generation chimeric antigen receptors (CARs), parallel CARs (pCARs), and adaptor CARs comprising intracellular signaling domains modified to achieve optimal signaling. Also provided herein are compositions and methods for increasing the anti-tumor efficacy and restimulation ability of CAR T cells, pCAR T cells, and adaptor CAR T cells.

Compositions for the treatment of cancer that include CAR T cells in which expression of FOXO3 expression is silenced are disclosed in various aspects. In various other aspects, methods for preventing or delaying a development of dysfunction in a CAR T cell associated with chronic antigen stimulation are described that include silencing the expression of FOXO3 by the CAR T cell.

Anti-BCMA antibodies and chimeric antigen receptors (CARs) are provided. Immune cells expressing the anti-BCMA CAR can be used to treat cancer. The anti-BCMA antibodies and CARs can recognize the extracellular domains of human BCMA. The anti-BCMA CAR T cells show specific cytotoxicity towards BCMA-positive target cells.

The present invention relates to antigen binding proteins specific for epithelial cell adhesion molecules (EpCAM), variants and fragments thereof, as well as multispecific antigen binding proteins that bind to EpCAM and other targets, such as bispecific T cell conjugates (BiTE). The invention also provides compositions comprising the antigen binding proteins, variants and fragments thereof, cells expressing / secreting them, methods of treatment employing the antigen binding proteins, variants and fragments thereof, and other uses thereof. In one embodiment, the cell is an immune cell, e.g., selected from the group consisting of T cells, macrophages, monocytes, and NK cells. In more specific embodiments, the cells are CAR T cells.

Provided are anti-idiotype antibodies that specifically recognize anti-BCMA antibody moieties, in particular, anti-BC-MA 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-BCMA CAR T cells. The disclosure further relates to uses of anti-idiotype antibodies for specifically activating such cells.

The invention discloses a reduction responsive nanoparticle armed chimeric antigen receptor T cell and a preparation method and application thereof, and belongs to the technical field of antigen receptor T cells, the chimeric antigen receptor T cell comprises a T cell expressing a chimeric antigen receptor aiming at a tumor-associated antigen; the plurality of reduction responsive hybrid nanoparticles are fixed on the outer surface of the T cell; according to the invention, the drug delivery system is accurately enriched at the tumor part by utilizing the targeting property of the CAR T cells to the tumor, and the release of the nanoparticles depends on a reducing microenvironment generated on the surface after the CAR T cells are activated, so that the fixed-point and controllable release of the drug is realized, and the toxic and side effects of systematic drug delivery are greatly reduced.