34 results about "CAR T-cell therapy" patented technology

Chimeric antigen receptors (CARs) and CAR-expressing T cells are provided that can specifically target cells that express an elevated level of a target antigen. Likewise, methods for specifically targeting cells that express elevated levels of antigen (e.g., cancer cells) with CAR T-cell therapies are provided.

The invention provides a CD19 targeted CAR (chimeric antigen receptor)-T cell, a preparation method and an application and relates to the field of immune cells. The activation capacity of T cells in CAR-T cell therapy can be improved, the problem of insufficient transfection efficiency can be solved, and the CAR-T cell has a high killing capacity for CD19. The CD19 targeted CAR-T cell expresses a CD19 targeted CAR gene on surface, and the CD19 targeted CAR gene is formed by connecting a single-chain antibody CD19ScFv of CD19, a hinge region and a transmembrane region of CD8, an intracellular signal structure of CD28, an intracellular signal structure of 4-1BB and an intracellular signal structural domain of CD3zeta in series, and the base sequence of the CD19 targeted CAR gene is shown as SEQ ID NO:2.

The invention relates to a tumor treatment method and particularly provides joint use of immunologic effector cells and radiation in tumor treatment, and a method of treating an individual with tumorsby joint use of immunologic effector cells and local radiation. The method provides no lymphocyte removal for the individual; the immunologic effector cells comprise a receptor to recognize tumor antigens to tumors. Tests prove that the method provided herein has significant antitumor effect for solid tumors; at the premise of pretreatment without removing lymphocytes, the joint treatment of CAR-T cell therapy and local radiotherapy with no lymphocyte removal helps attain better treatment effect than CAR-T treatment with lymphocyte removal; antitumor treatment effect is improved greatly.

The present disclosure relates to compositions and methods for reducing immune tolerance associated with CAR T cell therapy. Embodiments of the present disclosure include isolated nucleic acid sequence comprising a nucleic acid sequence that encodes modified programmed cell death protein 1 (PD-1) and a nucleic acid sequence that encodes chimeric antigen receptor (CAR).

The invention provides a CAR-T cell capable of efficiently and stably expressing an activated antibody and application thereof. Specifically, the genome of the transgenic T cell in the invention is stably integrated with expression cassettes containing nucleic acid sequences coding activated antibodies of chimeric antigen receptors and immune costimulatory molecules or receptors of the immune costimulatory molecules, wherein two ends of the expression cassettes contain inverted terminal repeats of transposons. In the genome of the pluripotent CAR-T cell, the expression cassettes of the activated antibodies are stably integrated via a transposon system, so the CAR-T cell has the activity of stably and efficiently expressing the activated antibodies on the premise that original killing activity of the CAR-T cell is maintained, and transfer-back cells are allowed to rapidly propagate at a tumor site. Meanwhile, a molecular brake system is introduced to ensure the security of CAR-T cell therapy, and transfer-back pluripotent CAR-T cells can be timely removed if necessary.

The invention discloses a marker used for in-vivo tracing and manual removal of CAR-T cells. The marker comprises a trace-linker 1 with a sequence as shown in SEQ ID No. 18, a trace-linker 2 with a sequence as shown in SEQ ID No. 19 and a trace-linker 3 with a sequence as shown in SEQ ID No. 19. The invention also discloses a CAR-T therapy vector including the marker and a construction method thereof. Moreover, the invention further discloses application of the marker to preparation of the CAR-T therapy vector and drugs used for treating triple-negative breast cancer. The marker provided by the invention can realize controllable in-vivo tracing, in-vitro separation and manual removal of CAR-T cells without influence on the tumor killing effect of the CAR-T cells, so the security of CAR-T cell therapy is greatly improved, and a powerful pool can be provided for deeper analysis of the process of CAR-T cell therapy. The vector provided by the invention can express a targeting chimeric antigen receptor of CD117 in human T lymphocytes, guides and activates killing effect of T lymphocytes on CD117 positive cells, and is applicable to treatment of triple-negative breast cancer in clinical practice.

Compositions disclosed herein, and methods of use thereof included those for inhibiting or reducing the incidence of cytokine release syndrome or cytokine storm in a subject undergoing CAR T-cell therapy, wherein the subjects are administered compositions comprising apoptotic cells or apoptotic cell supernatants. In certain instances compositions and methods of use thereof disclosed herein do notreduce the efficacy of the CAR T-cell cancer therapy. Disclosed herein are also compositions and methods of use thereof for decreasing or inhibiting cytokine production in a subject experiencing cytokine release syndrome or cytokine storm comprising administration of a composition comprising apoptotic cells or an apoptotic cell supernatant.

The present invention relates to the preparation and use in recipients of CAR-T cell-derived effector cells which are modified to limit their proliferation within the recipient. This is accomplished through the introduction of adducts into the nucleic acids of CAR-T cell-derived effector cells following expansion in vitro to provide expanded and activated CAR-T cell-derived effector cells that retain immunologic function, including the expression of one ore more cytokines.

The invention provides antibodies, antigen binding fragments thereof, chimeric antigen receptors (CARs), and engineered T cell receptors, polynucleotides encoding the same, and in vitro cells comprising the same. The polynucleotides, polypeptides, and in vitro cells described herein can be used in an engineered CAR T cell therapy for the treatment of a patient suffering from a cancer. In one embodiment, the polynucleotides, polypeptides, and in vitro cells described herein can be used for the treatment of multiple myeloma.

The invention discloses a preparation method of a cell for expressing an anti-CD22 chimeric antigen receptor and a PD-L1 blocking protein, an expression vector and application, and relates to the technical field of medical biology. A first nucleic acid encoding the anti-CD22 chimeric antigen receptor and a second nucleic acid encoding the PD-L1 blocking protein are inserted into the expression vector. By utilizing a CD22 target and a PD-L1 target and targeting an antibody or a fragment thereof of CD22, the T cell can efficiently and specifically target a tumor cell for expressing an antigen CD22; and the PD-L1 blocking protein can compete with endogenously expressed PD-1 to be combined with PD-L1 on a target cell, so that a PD-1/PD-L1 signal path is blocked, the action time of the T cell is prolonged, the tumor killing effect is improved, and the problem of immune tolerance of solid tumors to CAR T cell therapy is relieved.

Methods for reducing blood-brain barrier disruption in a subject treated with immunotherapy, the method comprising administering a recombinant GM-CSF antagonist to the subject. Methods for preserving blood-brain barrier integrity in a subject treated with immunotherapy, the method comprising administering a recombinant hGM-CSF antagonist to the subject. Methods for decreasing or preventing CAR-T cell therapy-induced neuroinflammation in a subject in need thereof, the method comprising administering a recombinant GM-CSF antagonist to the subject. Methods for preventing or reducing blood-brain barrier disruption in a subject treated with immunotherapy, the method comprising administering CAR-T cells having a GM-CSF gene knockout (GM-CSF^k/o CAR-T cells) to the subject.

The invention discloses a method for promoting in-vitro amplification of an umbilical cord blood T cell and maintaining a high-proportion TSCM subpopulation. The method comprises the steps that cycloastragenol, a cell factor IL-7 and a cell factor IL-15 are combined and added into an in-vitro culture solution of the T cell to promote the amplification of the T cell and maintain the high-proportionTSCM subpopulation. The method for promoting the in-vitro amplification of the umbilical cord blood T cell and maintaining the high-proportion TSCM subpopulation has the advantages that the high-proportion TSCM cell subpopulation can be maintained while the low-concentration CAG combined with the IL-7 and the IL-15 to promote the amplification of the umbilical cord blood derived T cell is successively explored; the novel in-vitro culture method lays an experimental foundation for the in-vitro long-term culture of the T cell and an immunization therapy containing a CAR-T cell therapy.

The invention provides a universal chimeric antigen receptor-T (CAR-T) cell as well as a preparation method and application thereof. The universal CAR-T cell can recognize polypeptide GCN and GCN-autoantibody affinity peptide fusion polypeptides, and can recognize and kill different self-reactive b cells in a targeted way under the guidance and regulation of different GCN-autoantibody affinity peptide fusion polypeptide guiders. The intensity or complete closure of an in vivo immune effect of the CAR-T cell can be very conveniently controlled, so that the reduction of other risks or side effects such as cytokine storms in general CAR-T cell therapy is facilitated; the universal CAR-T cell is different from conventional CAR-T cells need to be designed with different CARs aiming at differenttargets; therefore, time and cost are greatly reduced, and the success rate is increased.

Disclosed are means of protecting signaling integrity of T cells in cancer patients through reduction of neutrophil and other cellular induced oxidative stress. In one embodiment the FDA approved drug Mucomyst is administered at a concentration of 50-150 mg/kg to increase expression of T cell receptor (TCR)-zeta chain in patients with cancer. In other embodiments enhancement of CAR-T cell therapy is performed through modulation of inflammatory and oxidative stress in a tumor bearing patient.

The invention relates to a method for treating a side effect of chimeric antigen receptor (CAR) T cell therapy, the method comprising administering a mesenchymal stem cell (MSC) to a subject who has been or is being administered CAR T cell therapy.

The invention provides improved anti-BCMA CAR T cell compositions and methods for manufacturing anti-BCMA CAR T cell therapies. More particularly, the invention relates to improved methods of for manufacturing anti-BCMA CAR T cells that result in more potent, persistence, and efficacious adoptive T cell immunotherapies. In certain embodiments, the cells were manufactured from a subject that has a multiple myeloma or a lymphoma.

The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and administering to the patient a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

Provided herein are improved methods for robust TCR+ cell depletion and production of populations of TCR- cells, which can be beneficial to minimize the GvHD risk in patients receiving allogeneic CAR T cell therapy. Provided herein are methods that increase the efficiency of depleting TCR+ cells from a population of cells in order to significantly reduce any residual levels of TCR+ cells present in cell populations in which expression of endogenous TCR has been reduced or eliminated. Associated kits and cell populations are also provided.

CAR T cell therapies have shown promise in treating human blood cell cancer. The preparation of CAR T cells involves many complex, time consuming steps prior to infusion of the CAR T cells into a cancer patient. One step in the process to create CAR T cells often involves using magnetic separation technologies to isolate specific subsets of T cells prior to creating the CAR T cells. When using current magnetic separation technologies to remove undesired cell populations the recovery of the desired cell population can be as low as 50-70% or even lower and the procedures often take 30-60 minutes. In the case of autologous CAR T cell therapies such cell loss is often not acceptable. The present invention offers means to improve the recovery of desired cells to close to 100% very rapidly thus significantly improving a step in the manufacture of CART cells and in many cases will make such therapy possible for a larger patient population.

The present invention relates to T cell potentiators for use in CAR T cell therapy against hematologic tumors, such as acute myelogenous leukemia, and methods of using the same to enhance the effect of CAR T cell therapy. The method comprises treating T cells used in CAR T therapy in an in vitro culture process using a T cell potentiator. The T cell synergist provided by the invention can enhance migration of CAR T/NK cells to bone marrow, and improve the effect of CAR T cell therapy in removing tumors.