104 results about "Xenograft Transplantation" patented technology

The present invention is directed to transgenic animals (e.g., transgenic porcine animals) comprising multiple genetic modifications that advantageously render these animals suitable donors for xenotransplanation. The present invention extends to organs, organ fragments, tissues and cells derived from these animals and their therapeutic use. The present invention further extends to methods of making such animals. In certain embodiments, the transgenic animals (e.g., transgenic porcine animals) lack expression of alpha gal and incorporate and express at least four transgenes under the control of at least two promoters.

Presented is a therapeutic method to treat prostate carcinomas in mammals comprising the administration of cellular PAcP protein. Also presented is a method to diagnose androgen-insensitive prostate carcinomas by determining the expression level of cellular PAcP in the prostate carcinomas, a decrease in expression being indicative of androgen-insensitivity. A promoter region that is specifically expressed in prostate tissue is presented, as is a xenograft animal model that mimics human prostate carcinomas in the expression of cellular PAcP.

It has been discovered that there are at least two significant antigens present on the cells of animal species such as pigs that elicit an immune or inflammatory response immediately upon implantation into humans or contact with human serum. The first is an α-galactosyl (Gal) epitope, for example, Galα(1−>3)Galβ(1−>4)GlcNac (linear B type 2) or Galα(1−>3)Galβ(1−>4)Glc (linear B type 6). The second is an N-glycolylneuraminic acid (NeuGc) structure. By eliminating these epitopes, preferably by genetically engineering the animal so that the epitope is either not produced or is greatly reduced, or by chemical or enzymatic treatment of the animal's cells to remove the epitopes, it is possible to produce organs, tissues and cells suitable for xenotransplantation into humans. Cells can be rendered even more compatible by genetically engineering the animal to express a human complement regulator protein (inhibitor), such as CD59, on its cells, or to express an excess of a pig complement regulatory protein.

The present invention is directed to transgenic animals (e.g., transgenic porcine animals) comprising multiple genetic modifications that advantageously render these animals suitable donors for xenotransplanation. The present invention extends to organs, organ fragments, tissues and cells derived from these animals and their therapeutic use. The present invention further extends to methods of making such animals. In certain embodiments, the transgenic animals (e.g., transgenic porcine animals) lack expression of alpha gal and incorporate and express at least four transgenes under the control of at least two promoters.

The present invention provides ungulates, including pigs, expressing CTLA4-Ig, as well as tissue, organs, cells and cell lines derived from such animals. Such animals, tissues, organs and cells can be used in research and medical therapy, including xenotransplanation. In addition, methods are provided to prepare organs, tissues and cells expressing the CTLA4-Ig for use in xenotransplantation, and nucleic acid constructs and vectors useful therein.

The application provides methods of improving a rejection related symptom, reducing premature separation and methods of producing a compound of interest with an altered epitope profile are provided. Knockout pigs with a disrupted gene or genes, and porcine organs, tissues, and cells therefrom are provided.

Peptide constructs including a first peptide segment which includes an amino acid sequence associated with autoimmune disease, asthma, allergy or xeno- or allograft transplantation rejections bonded directly or via a linker or spacer to a second peptide which binds to T cells and which will redirect the immune response from a harmful Th1 response to a less harmful Th2 response, or which will bind to T cells to initiate, but not complete, an immune response causing the T cells to which the first peptide binds, to undergo anergy and apoptosis, are useful in treating autoimmune conditions. For instance, the peptide construct NGQEEKAGVVSTGLIGGGDSAFDVLSFTAEEKAGVYK (SEQ ID NO:14) wherein Th2 stimulating Peptide G (SEQ ID NO:15) is covalently linked, via spacer GGG, to cardiac myosin molecule My1 (SEQ ID NO:16), can be used for treatment or prevention of myocarditis.

The present invention relates to a method for culturing a 3-dimensional lung cancer organoid and a method for preparing a patient-derived xenograft animal model using the same. More specifically, the present invention relates to a method for culturing a 3-dimensional lung cancer organoid, a lung cancer organoid prepared by the method, a medium composition for culturing the lung cancer organoid, a method for preparing a xenograft animal model using the lung cancer organoid, a patient-derived lung cancer organoid xenograft animal model prepared by the method, and a method for analyzing therapeutic efficacy of an anticancer agent and a method for screening an anticancer agent, using the animal model.

A transgenic animal model for evaluating growth, survival and / or metastasis of xenotransplanted normal or tumor cells or tissue is disclosed, in which a human growth factor, hHGF stimulates growth in vivo of human cells or tissue. A strain of Tg mice on the C3H background that is immunocompromised as a result of a homozygous scid gene has been bred which express a nucleic acid encoding hHGF / SE The ectopically expressed hHGF / SF ligand significantly enhances growth of human tumor cell lines and explanted tumor cells or tissue that express the Met receptor for hHGF. Such animals also have an enlarged normal livers and greater than normal liver regenerative capacity. Any Met-expressing hHGF-dependent human cells, including hepatocytes and various stem cells can survive and grow in such animals.

The invention belongs to the field of rare cell or particle enrichment and screening, and relates to a spiral microchannel and a use method thereof, and a series-parallel installation structure. An inertial separation structure of a series-parallel spiral microchannel with reasonable cascading and application of multiple spiral microchannels are skillfully designed for the technical problem of thespiral microchannel in the field of sorting and enrichment of peripheral blood circulating tumor cells in a patient with a malignant tumor. Compared with the existing similar technology, the presentinvention not only has a good collection efficiency and processing flux of circulating tumor cells, but also maximizes the purity of circulating tumor cells and minimizes the loss of circulating tumorcells, and maintains the original phenotype of circulating tumor cells for sorting and enriching peripheral blood circulating tumor cells. The obtained cell suspension containing high-purity circulating tumor cells is particularly suitable for subsequent biomedical detection, genetic analysis, cell culture, xenograft tumor preparation, etc., and has extensive and far-reaching clinical practical application value.

A method for predictive engineering of a sample derived from a genetically optimized non-human donor suitable for xenotransplantation into a human having improved quality or performance is provided. The method includes constructing a training data set from a series of libraries, wherein at least one library in the series of libraries comprises genomic, proteomic, and research data specific to non-humans. The method includes developing a predictive machine learning model based on the constructed training data set. The method includes utilizing the predictive machine learning model to obtain a predicted quality or performance of a plurality of sequences for a candidate sample from the non-human donor specific to a human patient or patient population. The method includes selecting a subset of sequences for evaluation from the plurality of sequences based on the predicted quality or performance. The method includes designing candidate samples derived from the non-human donor using the selected subset of sequences. The method includes measuring a respective in silico performance of each designed candidate sample. The method includes selecting a designed candidate sample for manufacture based on the respective in silico performance of each designed candidate sample.

The present invention relates to an antigenic fusionprotein, which carries multiple Galα1,3Gal epitopes. The fusion protein according to the invention may also be comprised of a heavily glycosylated mucin part, which mediates binding to selecting, such as PSGL-1, and a part, which exhibits immunoglobulin properties, such as the Fc part of IgG. The fusionprotein according to the invention is preferably used as an absorber to prevent a hyperacute rejection of a xenotransplant, such as a pig tissue or organ transplanted into a human patient. In addition, the invention relates to a method for the prevention of a hyperacute rejection reaction in a patient who is to receive a xenotransplant.

The invention belongs to the technical field of biology, and particularly relates to tumor tissue implant liquid as well as a preparation method and application thereof. According to the tumor implantliquid provided by the invention, tissue homogenate after tumor formation of a human Ewing sarcoma cell line RD-ES is used as a tumor microenvironment simulation matrix, and EGF, hFGF, ITS, non-essential amino acids and L-glutamine are added as other components. The adhesive property of tumor tissues can be well improved, the tumor formation success rate of xenograft of human tumor cell strains can be greatly increased through verification of various tumor cells, and good effect on various tumor models is achieved. Besides, the preparation method provided by the invention is simple, low in cost, easy to operate and low in requirements for operators.

A method of determining disease diagnosis, progression and response to therapy through the use of xenograft animal models for determining cancer biomarkers is presented. In use, a tumor from a patient is transplanted into an animal model such as a mouse. Expression levels of biomarkers for a disease are assessed in the serum of the animal model. A personalized gene expression profile or biomarker gene signature may be obtained from the expression levels of the biomarkers which can be used to determine disease recurrence, progression and response to therapy.

The present invention relates to substituted azole derivatives and their use in the ex vivo expansion of CD34+ hematopoietic stem and progenitor cells (HSPC) in a biological sample, more particularlyin the expansion of these cells obtained from non-enriched, i.e., the mononuclear fraction of the biological sample. The present invention further describes the transplantation regimen of the expandedhematopoietic graft developed through xenotransplantation studies.

The present disclosure relates to making a hybrid pig-human thymic tissue and using the hybrid thymic tissue to induce tolerance in xenotransplantation. The hybrid thymic tissue can also be used for restoring or inducing immunocompetence in a recipient as well as restoring or promoting the thymus-dependent ability for T cell progenitors to develop into mature functional T cells in a recipient.

The present invention relates to substituted azole derivatives in combination with cytokines in the ex vivo expansion of CD34+ hematopoietic stem and progenitor cells (HSPC) in a biological sample, more particularly the expansion of these cells obtained from non-enriched, i.e., the mononuclear fraction of the biological sample. The present invention further describes the transplantation regimen of the expanded hematopoietic graft developed through xenotransplantation studies. In a preferred embodiment, the combination comprising the azole based compounds and cytokines selected from SCF, TPO, FLT-3L and IGFBP-2 and results in the expansion of expansion of CD45+CD34+CD38−CD45RA−CD90+ hematopoietic stem cells and / or CD45+CD34+CD38−CD45RA−CD90+CD49f+ hematopoietic stem cells and / or CD45+CD34+CD38−CD45RA− hematopoietic progenitor cells from the mononucleated cells isolated from umbilical cord blood.