104 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.

The present invention encompasses methods of cancer immunotherapy, and particularly methods of allogeneic cellular immunotherapy, used in populations of subjects having cancer who previously received an autologous cell therapy, had a response, and subsequently relapsed.

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 herein are, inter alia, methods for identifying dysfunctional natural killer (NK) cells in a subject with leukemia. Provided are methods for treating leukemia, including administering to the subject an effective amount of allogeneic NK cells.

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 relates to a method for performing a biological process on a liquid immune cell or an initial cell culture to obtain a treated cell culture, where the treated cell culture is intended for autologous or allogeneic cell therapy, where the biological process is performed on an integrated biological treatment system (1), wherein the biological process comprises a series of treatment steps wherein the treatment steps each comprise at least one operation wherein the biological process system (1) comprises a base structure (3) and a preconfigurable cartridge (4) wherein the biological process system (1) performs the operation of the biological process via interaction of the base structure (3) with the cartridge (4), wherein the cartridge (4) and the base structure (3) comprise a matching standardized interface (6) for interaction of the base structure (3) with a corresponding cartridge (4), wherein the biological process system (1) performs at least two operations of the biological process inside at least two differently preconfigured cartridges (4) by interaction of the base structure (3) with the cartridges (4) via the same base structure interface (7) and / or the same base structure interface (7) and a mating cartridge interface (8).

The present invention discloses an engineered cell and its application, wherein the engineered cell lacks or reduces the expression of HLA-A protein and / or HLA-B protein compared with the wild type. The engineered cell disclosed in the present invention can significantly reduce the immune rejection reaction after human hematopoietic cell infusion, while significantly improving the implantation rate and long-term reconstruction capacity in vivo. The cell will significantly expand the use of existing cord blood and bone marrow donor banks, reduce the need to recruit a large number of donors to match recipients, increase the probability of HLA matching donors, and thus expand the infusion of clinical-grade allogeneic cells. As a source of universal cells, engineered cells can realize HLA-matched off-the-shelf cell therapy, which has important prospects for clinical transplantation treatment.

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).

Described are methods for the production and use of cryopreservable double negative T cells (DNTs) for the treatment of cancer as an off-the-shelf cellular therapy. A sample population of DNTs is expanded using DNTs from one or more donors. The expanded population of DNTs from different donors does not exhibit alloreactivity against allogenic cells in the expanded population. The expanded populations of DNTs can be long-term stored as cryopreserved products.

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.

Disclosed herein are methods of selecting an allogeneic T cell line for therapeutic administration to a patient carrying / suffering from or suspected of carrying / suffering from a pathogen or cancer. Also disclosed are methods of selecting a donor from which an allogeneic T cell line is obtained for therapeutic administration to a patient carrying / suffering from or suspected of carrying / suffering from a pathogen or cancer.

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.

To provide methods for treating cancer.SOLUTION: Provided are methods comprising the administration of donor-derived allogeneic γδ-T cells (gamma / delta-T cells) to a subject. In such methods, at least one lymphodepletion treatment or a Hematopoietic Stem Cell (HSC) transplant is administered to the subject, followed by the subsequent administration of donor-derived allogeneic γδ-T cells. The methods also comprise expanding the donor-derived allogeneic γδ-T cells ex vivo prior to administration to the subject. Such methods comprise exposing donor-derived allogeneic γδ-T cells to one or more γδ-T cell expansion compounds. Such a therapy induces an antitumor response in the subject.SELECTED DRAWING: None

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.

Provided herein are engineered T cells expressing a heterologous chimeric antigen receptor (CAR) and deficient in certain T cell receptor (TCR) and major histocompatibility complex (MHC) genes, useful for allogeneic CAR T cell therapy. Also provided are methods of producing such engineered T cells.

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