119 results about "Allogeneic cell" patented technology

Isolated cells are described that are not embryonic stem cells, not embryonic germ cells, and not germ cells. The cells can differentiate into at least one cell type of each of at least two of the endodermal, ectodermal, and mesodermal lineages. The cells do not provoke a harmful immune response. The cells can modulate immune responses. As an example, the cells can suppress an immune response in a host engendered by allogeneic cells, tissues, and organs. Methods are described for using the cells, by themselves or adjunctively, to treat subjects. For instance, the cells can be used adjunctively for immunosuppression in transplant therapy. Methods for obtaining the cells and compositions for using them also are described.

A method of manipulating allogeneic cells for use in allogeneic cell therapy protocols is described. The method provides a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism called the “Mirror Effect”. In contrast to current allogeneic cell therapy protocols where T-cells in the graft mediate the beneficial graft vs. tumor (GVT) and detrimental graft vs. host (GVH) effects, the allogeneic cells of the present invention stimulate host T-cells to mediate the “mirror” of these effects. The mirror of the GVT effect is the host vs. tumor (HVT) effect. The “mirror” of the GVH effect is the host vs. graft (HVG) effect. The effectiveness and widespread application of the anti-tumor GVT effect is limited by the severe toxicity of the GVH effect. In the present invention, the anti-tumor HVT effect occurs in conjunction with a non-toxic HVG rejection effect. The highly activated allogeneic cells of the invention can be used to stimulate host immunity in a complete HLA mis-matched setting in patients that have not had a prior bone marrow transplant or received chemotherapy and / or radiation conditioning regimens.

The present invention relates to an improved scaffold which is constructed to mimic the architecture of the native hair follicle. The present invention also relates to the use of specific compositions and methods of manufacture to produce scaffolds that combine biocompatibility with the desired rates of bioabsorption. In another embodiment, the present invention relates to a process for manufacturing a biomimetic hair follicle graft and a method for seeding the graft with cells and implanting the graft into the skin where the growth of a new hair shaft is desired. A further embodiment of the present invention relates to a method for hair multiplication in which cells are multiplied in culture and aliquoted into a multitude of bioabsorbable scaffolds in combination with cultured keratinocytes or other allogenic cells.

The present invention provides a method of transplanting hematopoietic cells between genetically unrelated individuals, comprising administering to the recipient, in combination with the administration of the hematopoietic cells, an amount of mononuclear cells which are treated so as to substantially reduce their ability to cause graft versus host disease while they retain their ability to proliferate in the recipient. The treated mononuclear cells can facilitate engraftment of hematopoietic cells when transplanted in combination with hematopoietic cells, treat or prevent infections, and treat cancer.

The invention belongs to the field of immunotherapy and relates to a universal CAR-T cell and a preparation method and application thereof. In the universal CAR-T cell, the functions of a T cell antigen receptor (TCR) and major histocompatibility complexes (MHC I and MHC II) in the T cell are inhibited while multi-gene knockout is performed; a gene encoding the TCR includes TRAC and / or TRBC; genesencoding the major histocompatibility complexes include HLA-A, B2MH and CIITA. The universal CAR-T cell can target relevant markers of specific tumors and inactivate the functions of the TCR and theMHC on the cell surface, can reduce immunological rejection caused by allogeneic cell therapy and safely and effectively remove tumor cells in the diseased human body, is not affected by the disease or a treatment mode of a patient in use and can be prepared at any time, treatment can be provided at the optimum time, and treatment effectiveness is ensured.

Isolated cells are described that are not embryonic stem cells, not embryonic germ cells, and not germ cells. The cells can differentiate into at least one cell type of each of at least two of the endodermal, ectodermal, and mesodermal lineages. The cells do not provoke a harmful immune response. The cells can modulate immune responses. As an example, the cells can suppress an immune response in a host engendered by allogeneic cells, tissues, and organs. Methods are described for using the cells, by themselves or adjunctively, to treat subjects. For instance, the cells can be used adjunctively for immunosuppression in transplant therapy. Methods for obtaining the cells and compositions for using them also are described.

A method of treating a disease, such as cancer, by administering to a subject in need of such treatment an effective amount of allogeneic T cells with a MHC unrestricted chimeric receptor short time after partial lymphodepletion. The method also comprises administering one or more agents that delay egression of the allogeneic T cells from lymph nodes of said subject during adoptive transfer of said allogeneic T cells to the subject by trapping the T cells in the lymph nodes.

The invention disclosed herein relates generally to immunotherapy and, more specifically, to the use of immunotherapy for treating tumors and pathogen infected tissues by first priming patients with allogeneic cells designed to be rejected by a Th1 mediated mechanism, then inducing necrosis or apoptosis in a tumor or pathogen infected lesion by methods such as cryotherapy, irreversible electroporation, chemotherapy, radiation therapy, ultrasound therapy, ethanol chemoablation, microwave thermal ablation, radiofrequency energy or a combination thereof applied against at least a portion of the tumor or pathogen infected tissue, and then delivering one or more doses of allogeneic cells (e.g., Th1 cells) within or proximate to the tumor or pathogen-infected tissue in the primed patient. The present invention provides an immunotherapeutic strategy to develop de-novo systemic (adaptive) immunity to a tumor or pathogen.

Disclosed are allogeneic cells useful for the treatment of cancer in a universal donor, off the shelf, manner. In one embodiment of the invention cord blood derived T cell progenitors are matured with anti-CD3 and anti-CD28, interleukin-7 and transfected with a construct encoding a chimeric antigen receptor (CAR) targeting a tumor antigen or a tumor endothelial associated antigen on the antigen binding domain. The intracellular domain containing CD3 zeta chain and at least one shRNA domain encoding a transcript which generates at least one siRNA capable of inhibiting expression of HLA I and / or HLA II. In another embodiment mesenchymal stem cells are transfected with CAR to enhance migration into tumors and induce tumor death, reduction of inflammation, or immune sensitization. In another embodiment universal donor CAR-MSC are disclosed.

The invention disclosed herein relates generally to immunotherapy and, more specifically, to the use of immunotherapy for treating tumors and pathogen infected tissues by first priming patients with allogeneic cells designed to be rejected by a Th1 mediated mechanism, then inducing necrosis or apoptosis in a tumor or pathogen infected lesion by methods such as cryotherapy, irreversible electroporation, chemotherapy, radiation therapy, ultrasound therapy, ethanol chemoablation, microwave thermal ablation, radiofrequency energy or a combination thereof applied against at least a portion of the tumor or pathogen infected tissue, and then delivering one or more doses of allogeneic cells (e.g., Th1 cells) within or proximate to the tumor or pathogen-infected tissue in the primed patient. The present invention provides an immunotherapeutic strategy to develop de-novo systemic (adaptive) immunity to a tumor or pathogen.

A method for stimulating the immune system in immunocompromised patients in order to treat opportunistic infection. The method involves the infusion of intentionally mismatched allogeneic cells. In order to prevent graft vs. host disease complications, the allogeneic cells can be irradiated prior to infusion.

This invention provides methods and compositions for treating tumors. The cell population is made up of alloactivated lymphocytes from the patient or from one or more third-party donors that are alloactivated in a mixed lymphocyte culture. It can be placed into the tumor bed, or combined with tumor-associated antigen for administration to a distal site as a vaccine. The compositions recruit activated participation of the host Immune system, which then reacts against the tumor and provides a level of ongoing protection. Employing multiple third party donor cells confers particular advantages in terms of effectiveness, timing, and ease of use.

The invention provides a composition for stimulating an immune response in a patient having different types of cancer including those having adenocarcinoma comprising a combination of allogeneic tumor cells and / or tumor stem cells that are selected on the basis of secreting at least one immunosuppressive agent, e.g., TGF-β, and that are genetically modified to reduce or inhibit the expression of said at least one immunosuppressive agent, e.g., TGF-β, and that collectively express a spectrum of tumor associated antigens representative of colon, breast, lung, prostate, pancreas, kidney, endometrium, cervix, ovary, thyroid, and other glandular tissue carcinomas, as well as squamous, melanoma, central nervous system, and lymphomas and a physiologically acceptable carrier. The adenocarcinoma can be, for example, colon, breast, lung, prostate, pancreas, kidney, endometrium, cervix, ovary, thyroid, or other glandular tissue, as well as squamous, melanoma, central nervous system, and lymphomas. The invention also provides a composition containing said combination of allogeneic tumor cells and or tumor stem cells and an allogeneic cell expressing a cytokme or an antibody that inhibits an immune suppressive molecule.

T cells of a graft recipient are stimulated in-vitro by cells of a graft donor or by cells which express dominant MHC-molecules, while they are transduced with immuno-modulatory genes using gene transfer. Following the gene transfer the transduced T cells start to express immuno-modulatory genes. The gene transfer can be accomplished using retroviruses, other viral vector systems or liposomes. Due to the chosen set-up of the experiment, which leads to the generation and expansion of allospecific T cells, the T cells migrate, after the in-vivo application, specifically into the allogeneic graft as well as into the draining lymph nodes and are then able to express the immuno-modulatory genes there. Rejection of allogeneic grafts (cells, tissues, organs) can be successfully prevented, tolerance towards allogeneic grafts can be induced and maintained.

The invention here relates to a product comprised of a cell line or lines intended for use as an allogeneic immunotherapy agent for the treatment of cancer in mammals and humans. All of the studies of cell-based cancer vaccines to date have one feature in common, namely the intention to use cells that contain at least some TSAs and / or TAAs that are shared with the antigens present in patients' tumour. In each case, tumour cells are utilised as the starting point on the premise that only tumour cells will contain TSAs or TAAs of relevance, and the tissue origins of the cells are matched to the tumour site in patients. A primary aspect of the invention is the use of immortalised normal, non-malignant cells as the basis of an allogeneic cell cancer vaccine. Normal cells do not possess TSAs or relevant concentrations of TAAs and hence it is surprising that normal cells are effective as anti-cancer vaccines. For prostate cancer, for example, a vaccine may be based on one or a combination of different immortalised normal cell lines derived from the prostate. The cell lines are lethally irradiated utilising gamma irradiation at 50–300 Gy to ensure that they are replication incompetent prior to use in the mammal or human.

The present invention provides methods for preventing the allogeneic immune rejection of allogeneic cells, such as cells derived from human Embryonic Stem Cells (hESCs), without suppressing the entire immune system. Also provided a vector containing a CTLA4-Ig and PD-L1 expression cassette, and compositions containing a CTLA4-Ig and PD-L1 for use in preventing allogeneic immune rejection of allogeneic cells.

A method of manipulating allogeneic cells for use in allogeneic cell therapy protocols is described. The method provides a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism called the “Mirror Effect”. In contrast to current allogeneic cell therapy protocols where T-cells in the graft mediate the beneficial graft vs. tumor (GVT) and detrimental graft vs. host (GVH) effects, the allogeneic cells of the present invention stimulate host T-cells to mediate the “mirror” of these effects. The mirror of the GVT effect is the host vs. tumor (HVT) effect. The “mirror” of the GVH effect is the host vs. graft (HVG) effect. The effectiveness and widespread application of the anti-tumor GVT effect is limited by the severe toxicity of the GVH effect. In the present invention, the anti-tumor HVT effect occurs in conjunction with a non-toxic HVG rejection effect. The highly activated allogeneic cells of the invention can be used to stimulate host immunity in a complete HLA mis-matched setting in patients that have not had a prior bone marrow transplant or received chemotherapy and / or radiation conditioning regimens.

Disclosed herein are methods of selecting an allogeneic T cell line for therapeutic administration to a patient having or suspected of having a pathogen or cancer. Also disclosed are methods of selecting a donor from whom to derive an allogeneic T cell line for therapeutic administration to a patient having or suspected of having a pathogen or cancer.

The invention relates to a stem cell bank system and a method of the stem cell bank system for transferring a cell resource. The stem cell bank system comprises a cell collecting module, a cell generating module, a cell quality testing module, a cell storage module and a cell information module. Each module of the stem cell bank system is independent in operation, distinct in function and convenient to manage; the information among the modules is transferred in real time, so that the cell information is immediately and accurately recorded into the cell information module, classified and stored to conveniently track the cell in the system and circulate cell information in the future; autogenous and allogeneic cells are collected, produced, tested and stored to avoid cross contamination among the cells; the quality of the cells is ensured; and the cell information module achieves real-time interaction of the cell information. A user can enquire and primarily screen the cells in the system through the system according to the needs, strictly controls circulation of the cells, and is responsible to patients. Meanwhile, the information of the user is stored so as to be convenient for track and visit after sale.

Novel antigen-presenting cells, including but not limited to dendritic cells, that are loaded with antigens from dead or dying cells including allogenic cell lines, and the methods for making such antigen-presenting cells are described. These loaded antigen-presenting cells induce therapeutic immune responses in humans. Such loaded antigen-presenting cells are useful in the management of cancer. Antigen-loaded dendritic cells prepared as described here can prime naïve T cells to differentiate into effector cells able to recognize multiple and / or shared tumor antigens that are expressed either on the tumor cells that are used to load the dendritic cells and / or on other tumor cells. The cytotoxic T cells generated by exposure to antigen-loaded dendritic cells prepared as described here can be used in adoptive therapy. This induction of responses against multiple antigens shared between different cells, for instance tumor cells, as described here is important as it leads to broad immune responses.

The present invention relates to an implantable composition for treating a damaged tissue and a method for inducing an in vivo migration of a cell for treatment to a damaged tissue region. The present invention treats the damaged tissue by inducing / promoting homing of a cell for tissue generation by implanting a biodegradable scaffold reacted with chemotactic factors (for example, IL-8 or MIP-3±) to a damaged location (for example, joint cartilage or skin). Thus, the composition of the present invention can not only be applied to the treatment of a damaged bone tissue, a joint cartilage, or a skin tissue more conveniently and efficiently compared to the conventional technology, but can also be used as a useful treatment supplement agent in cell treatment using allogeneic cell by enabling efficient utilization of cell resources for treatment, the cell resources which are high in scarcity.

The invention relates to the technical field of cell culture media, and discloses a cell culture medium beneficial to in-vitro culture of autologous bone marrow mesenchymal stem cells. The cell culture medium is characterized in that an autologous PL blood platelet lysis buffer is added during preparation. The autologous bone marrow mesenchymal stem cells are cultured by using the cell culture medium added with the PL blood platelet lysis buffer so as to ensure that the cell proliferation capability of cells in in-vitro culture; and meanwhile, a phenomenon that the mesenchymal stem cells cannot be affected by exogenous pollution in in-vitro culture and amplification can be ensured, the immunological rejection of allogeneic cells generated in a disease treatment process can also be avoided, and an application of treating self-diseases by using autologous cells clinically can be facilitated.

The present invention provides a method for assessing stem cell transplant in a protein-containing sample using multi-dimensional protein separation. Such multi-dimensional separation techniques include chromatography, electrophoresis and mass spectrometry. A protein-containing sample may comprise body fluids such as blood and serum but may also include a cell, tissue or organ. Identification of a protein present in the donor and the transplant recipient but not in the recipient sample before transplant indicates that the stem cell is grafted.

The invention discloses a preparation method of multiple acellular materials modified with nucleus pulposus cells for porcine small intestinal submucosa (SIS). The method specially comprises the following steps: stripping the porcine SIS tissues; carrying out treatment on the stripped porcine SIS tissues through a normal saline buffer solution containing a protease inhibitor, an organic solvent solution, a PBS (Phosphate Buffered Saline) buffer solution containing Triton X, a PBS buffer solution containing SDS (Sodium Dodecyl Sulfate) and a PBS buffer solution containing DNA enzyme to obtain acellular SIS materials; performing ball milling and pulverization on the acellular SIS materials to obtain micro-particles with diameter of 200mu m; carrying out co-culture on the micro-particles andseparated nucleus pulposus cells and then carrying out decellularization treatment again so as to obtain injectable multiple acellular nucleus pulposus repairing materials. According to the preparation method of the multiple acellular materials modified with the nucleus pulposus cells for the porcine SIS disclosed by the invention, the completeness of original ECM (Extra Cellular Matrix) can be preserved while allogeneic cells or heterologous cells with immunoreactivity are removed at the same time, and the preparation method of the multiple acellular materials modified with the nucleus pulposus cells for the porcine SIS has an good extracellular micro-environment, bio-factors, biomechanical properties and the like, and can simulate a growth environment of nucleus pulposus cells in normalphysiological conditions to a maximum limit.

The present invention relates to the use of “off-the-shelf” allogeneic therapeutic cells for immunotherapy in conjunction with chemotherapy to treat patients with cancer. In particular, the inventors develop a method of engineering allogeneic T-cell resistant to chemotherapeutic agents. The therapeutic benefits afforded by this strategy should be enhanced by the synergistic effects between chemotherapy and immunotherapy. In particular, the present invention relates to a method for modifying T-cells by inactivating at least one gene encoding T-cell receptor component and by modifying said T-cells to confer drug resistance. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer.

The development of graft versus host disease in a mammalian patient undergoing cell transplantation therapy for treatment of a bone marrow mediated disease, is prevented or alleviated by subjecting at least the T-cells of the allogeneic cell transplantation composition, extracorporeally, to oxidative stress, in appropriate dosage amounts, such as bubbling a gaseous mixture of ozone and oxygen through a suspension of the T-cells. The process may also include irradiation of the cells with UV light, simultaneously with the application of the oxidative stress. The oxidative stress induces reduced inflammatory cytokine production and a reduced proliferative response in the T-cells.

The invention belongs to the technical field of cell sorting, and concretely discloses a magnetic cell sorting apparatus based on nanoferritin adsorption. The sorting apparatus comprises nanoferritin particles and a laminar aseptic sealed chamber, and a sample bottle, and a cell sorting tank having a magnetic field, a nano-iron particle eluting device, a multi-cell automatic culturing system, a recovering, rinsing and loading device, a control system for controlling the temperature, humidity and air cleanliness in the sealed chamber, and a cell sorting monitoring system for monitoring and displaying the whole cell sorting process, which are sequentially connected with the sample bottle through a connecting tube, are arranged in the sealed chamber. The sorting apparatus has a good sorting effect, can effectively prevent the cross contamination among patients and the hybridization of tumor cells, can reach high-efficiency, high-quality and zero-pollution automatic cell sorting, is in favor of reducing the medical cost, is also convenient for the allogeneic cell sorting, is suitable for more diseases, and has wide uses.