73 results about "Allogeneic cell" patented technology

Provided herein are engineered immune cells and populations thereof for administration to patients to treat cancer (e.g., solid tumors or liquid tumors) and other conditions. The cells are engineered to functionally express a reduced level of one or more of RFX5, NLRC5, TAP2, β2m, TRAC, RFXAP, CIITA and RFXANK. The cells optionally are further engineered to express one or more than one additional protein such as an antigen binding protein (e.g., a chimeric antigen receptor (CAR) or T cell receptor) to target tumor cells or other damaged cells in the patient and / or to express other genes at a reduced level. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering the cells and the compositions.

Several embodiments disclosed herein relate to methods and compositions for enhanced expansion of NK cells in culture, through the repeated co-culturing of NK cells with feeder cells and the selective use of stimulatory interleukins. In several embodiments, the methods utilize one or more soluble interleukins as culture media supplements at one or more time points during expansion of the NK cell, or other immune cell, which results in a highly expanded and highly cytotoxic population of cells, for use in, for example allogeneic cellular immunotherapy.

Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. The derivative cells provided herein have stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also provided are therapeutic compositions and uses thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors in combination therapies.

The present invention provides methods for producing allogeneic T cells comprising the use of an engineered nuclease under the control of a controllable promoter. By preparing T cells with an inducible nuclease, a large number of cells can be prepared, each of the cells having the ability to produce a desired nuclease alone. These cells may then be modified as desired by introducing a gene of interest, or undesirable genes may be knocked out. Also provided herein are allogeneic T cells for use in various therapeutic applications.

The present invention relates to engineered immune cells expressing a chimeric antigen receptor (anti-mesothelin CAR) specific for mesothelin (MLSN) and their use in the treatment of solid tumors, particularly suitable for allogeneic cell immunotherapy.

We have discovered that allogeneic HSC-engineered human iNKT (3rdHSC-iNKT) cells display potent anti-GvHD functions, by eliminating antigen-presenting myeloid cells in vitro and in xenograft models, without negatively impacting tumor eradication by allogeneic T cells in preclinical models of lymphoma and leukemia. The 3rdHSC-iNKT cells closely resembled the CD4−CD8− / + subsets of endogenous human iNKT cells in phenotype and functionality. Embodiments of the invention harness these discoveries in new methods and materials for alleviating graft versus host disease.

The present invention provides methods and compositions for treating EBV-related disorders. [Solution] A method is provided for treating or preventing an EBV-related disease, disorder, or condition in a subject, comprising the steps of (a) administering to the subject a first population of allogeneic T cells that bind to or recognize a first epitope of an EBV antigen; and (b) administering to the subject a second population of allogeneic T cells that bind to or recognize a second epitope of the EBV antigen or a further EBV antigen, thereby treating or preventing the EBV-related disease, disorder, or condition in the subject.

In the various aspects and embodiments, the present disclosure provides cell populations or cell "banks" thereof to provide immune compatible, allogeneic cell therapies. In the various aspects and embodiments, the cell populations and progeny thereof maintain sufficient HLA Class I and HLA Class II functionalities, while facilitating patient matching to prevent or reduce graft versus host disease (GVHD) or graft rejection. The disclosure further provides methods for creating the populations by gene editing, and methods for cell therapy involving cells or tissues derived from the cell populations (including but not limited to hematopoietic stem cells, or "HSCs", progenitors, or progenies thereof).

This disclosure provides compositions and methods of making cells, such as allogenic cells, engineered to evade host immune responses, particularly from T cells and natural killer cells, and populations thereof. The compositions and methods for making engineered cells include making genetic modifications that reduce or eliminate the expression of an NKG2D ligand or integrate sequences encoding HLA molecules, such as HLA-E or HLA-G. Such modifications can enhance the survival of the engineered cells within a host without impeding their ability to differentiate into functional cell types, such as cardiomyocytes.

The present disclosure provides methods and compositions for culturing and engineering of allogeneic B lineage cell populations.

The present disclosure relates to RNAi DNA oligonucleotides for the suppression of an immune response and use in methods of one step construction of allogenic CAR cells capable of avoiding a host rejection.

This invention relates to the selective removal of activated T cells using a monovalent antibody or its antigen-binding fragment, which includes heavy chain variable regions and light chain variable regions of an antibody that specifically binds to CD3. In one embodiment of the present invention, the monovalent anti-CD3 antibody or its antigen-binding fragment is useful as a T cell removal agent or T cell immunosuppressant because it can selectively remove only activated T cells without affecting non-activated T cells. In particular, this invention is useful for the prevention or treatment of T cell-mediated autoimmune diseases, graft-versus-host diseases, or organ transplant rejection, as well as for the prevention of graft-versus-host disease (GVHD) side effects in allogeneic CAR-T cell therapy.

This disclosure provides methods and populations of cells, engineered to modulate the expression of select genes and thereby reduce natural killer cell mediated cytotoxicity. For example, this disclosure provides engineered cells equipped with one or more heterologous nucleic acid sequences encoding polypeptides that, when expressed, impede the typical cytotoxicity of natural killer cells as compared to comparable cell devoid of heterologous nucleic acid sequence.

The present disclosure relates, at least in part, to compositions comprising constant natural killer T (iNKT) cells (e.g., unmodified allogeneic iNKT cells), and uses of the compositions comprising the iNKT cells to treat a disease or a symptom or complication of a disease (e.g., a viral infection, a disease secondary to a primary disease (e.g., a neurological disease). The present invention relates to a method for treating acute respiratory distress syndrome (ARDS) and / or organ failure associated therewith (e.g., viral infection).

Provided herein are CD70-targeted chimeric antigen receptors (CARs), genetically engineered cells such as T cells containing the same, and related methods and uses of the genetically engineered cells in allogeneic cell therapy. Also provided are T cells that are genetically engineered with a CAR, such as a CD70-targeted CAR, and are further genetically engineered by one or more strategies to reduce host immune recognition of the engineered T cells, such as by heterologous expression of one or more additional transgenes and by genetic disruption to reduce or eliminate expression or one or more endogenous protein. Also provided are methods of making and using the engineered T cells for cell therapy, including in connection with cancer immunotherapy comprising adoptive transfer of the engineered T cells.

Disclosed are chimeric stimulatory receptors (CSRs), cellular compositions comprising the CSRs, methods of making the same, and methods of using the same for treating a disease or condition in a subject.

Provided are methods and compositions including for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. Also provided are derivative cells having stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also provided are therapeutic compositions and the use thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors in combination therapies.

The present disclosure provides a method for judging the level of immune rejection between heterologous cells, tissues or organs, and relates to the field of biological medicine. The method provided by the present disclosure can quickly and objectively compare the interspecies relative phagocytosis rate of phagocytes in a single experiment, and provides a new way for evaluating and researching the level of immune rejection between heterologous cells, tissues or organs.

Provided are methods and compositions conditioning a patient for an allogeneic transplantation, wherein the patient's hematopoietic stem cells (HSCs) are depleted with an HSC-depleting composition and the patient is then administered allogeneic cells selected from bone marrow cells, umbilical cord blood cells, hematopoietic stem and progenitor cells (HSPCs), peripheral blood CD34+ cells, and peripheral blood CD34+ and CD90+ cells; optionally the patient is also administered a medicament selected from the group consisting of a T-cell depleting or inhibiting antibody or antibody fragment, NK-cell depleting or inhibiting antibody or antibody fragment, immunosuppressive drug, and any combination thereof. The HSC-depleting composition comprises a compound selected from the group consisting of: an antibody or antibody fragment with specific binding affinity to a protein displayed at the HSC surface, a conjugate comprising an HSC-recognition molecule and a toxin, and any combination thereof.

A method and composition is described of treating metastatic colorectal cancer cells comprises administering activated allogeneic CD4+ T-cells to the colorectal cancer cells; and administering at least one immune checkpoint inhibitor to the colorectal cancer cells.

Method for performing a bioprocess to obtain processed cell cultures, wherein the processed cell cultures are destined for autologous or allogenic cell therapy, wherein the bioprocess is performed on an integrated bioprocessing system, wherein the bioprocess comprises a sequence of processing steps, wherein the processing steps each comprise at least one operation, wherein the bioprocess system comprises a base structure and preconfigurable cartridges, wherein the bioprocess system performs operations of the bioprocess via an interaction of the base structure with the cartridges, wherein the cartridges and the base structure comprise matching standardized interfaces for an interaction of the base structure with the respective cartridge, wherein the bioprocess system performs at least two operations of the bioprocess inside at least two differently preconfigured cartridges by an interaction of the base structure with the cartridges via the same base structure interface and / or identical base structure interfaces and matching cartridge interfaces.

A method and composition is described of treating metastatic colorectal cancer in a patient, comprises administering activated allogeneic CD4+ T-cells to a patient; and administering at least one immune checkpoint inhibitor to the patient

Provided herein are genetically engineered T cells containing a chimeric antigen receptor (CARs), and related methods and uses thereof in allogeneic cell therapy. In some embodiments, the T cells are genetically engineered with a CAR and are further genetically engineered by one or more strategies to reduce host immune recognition of the engineered T cells, such as by heterologous expression of one or more additional transgenes and by genetic disruption to reduce or eliminate expression or one or more endogenous protein. Also provided are cell compositions containing the engineered T cells, and related methods, kits and systems for producing the engineered T cells. Also provided are methods of making and using the engineered T cells for cell therapy, including in connection with cancer immunotherapy comprising adoptive transfer of the engineered T cells.

The invention relates to vaccination with immune-isolated cells producing immunomodulators. Provided herein are vaccine compositions containing at least one retrievable biocompatible macrocapsule containing immune-isolated allogeneic cells that secrete an immunomodulator, such as GM-CSF (granulocyte-macrophage colony stimulating factor), and an antigen component (e.g., autologous tumor cells or infectious factors). Also provided herein are kits and pharmaceutical compositions containing the vaccine compositions and said products for use in methods of therapeutic or prophylactic vaccination against tumors or infectious factors.

Provided are methods and compositions conditioning a patient for an allogeneic transplantation, wherein the patient's hematopoietic stem cells (HSCs) are depleted with an HSC-depleting composition and the patient is then administered allogeneic cells selected from bone marrow cells, umbilical cord blood cells, hematopoietic stem and progenitor cells (HSPCs), peripheral blood CD34+cells, and peripheral blood CD34+ and CD90+ cells; optionally the patient is also administered a medicament selected from the group consisting of a T-cell depleting or inhibiting antibody or antibody fragment, NK-cell depleting or inhibiting antibody or antibody fragment, immunosuppressive drug, and any combination thereof. The HSC-depleting composition comprises a compound selected from the group consisting of: an antibody or antibody fragment with specific binding affinity to a protein displayed at the HSC surface, a conjugate comprising an HSC-recognition molecule and a toxin, and any combination thereof.

Various cells, stem cells, and stem cell components, including associated methods of generating and using such cells are provided. In one aspect, for example, an isolated cell that is capable of self-renewal and culture expansion and is obtained from a subepithelial layer of a mammalian umbilical cord tissue. Such an isolated cell expresses at least three cell markers selected from CD29, CD73, CD90, CD166, SSEA4, CD9, CD44, CD146, or CD105, and does not express at least three cell markers selected from CD45, CD34, CD14, CD79, CD106, CD86, CD80, CD19, CD117, Stro-1, or HLA-DR.

The present disclosure provides allogeneic cells having a reduced risk of graft versus host disease (GVHD) and a reduced risk of CD8 and NK cell rejection when used, for example, in the treatment of a disease in a patient, such as cancer and / or autoimmune disease. These allogeneic cells may be genetically engineered to reduce the expression or activity of CD58. Methods of making and using such allogeneic cells are also provided.

The purpose of the present disclosure is to provide highly versatile, ready-to-deliver allogenic T cells for novel coronavirus infection, and a production method therefor. The present invention provides: a method for producing a cell population for the treatment and / or prevention of SARS-CoV-2 infection and including T cells or precursor T cells that express a human T cell receptor (TCR) specific to SARS-CoV-2, said method comprising a step for causing the expression of one or more human TCRs specific to SARS-CoV-2 in T cells or precursor T cells in vitro; and a cell population for the treatment and / or prevention of SARS-CoV-2 infection and produced via said method, said cell population comprising allogenically derived T cells or precursor T cells.

The present disclosure, at least in part, relates to compositions comprising invariant natural kill T (iNKT) cells (e.g., unmodified, allogeneic iNKT cells), and methods of using the compositions comprising the iNKT cells for treating a disease, or a symptom or complication of a disease (e.g., viral infection, acute respiratory distress syndrome (ARDS) secondary to a primary disease (e.g., viral infection) and / or its associated organ failure).