52 results about "Heterografts" patented technology

Described herein are compositions and methods of use of radionuclide-antibody conjugates (for RAIT) and drug-antibody conjugates (ADC). The combination of RAIT and ADC was more efficacious than either RAIT alone, ADC alone, or the sum of effects of RAIT and ADC. The unexpected synergy resulted in decreased tumor growth rate and increased survival, with a high incidence of tumor-free survival in Capan-1 human pancreatic cancer xenografts in nude mice.

An implantable graft, which may be inserted into a fistula tract to occlude the primary opening of the fistula, is provided. To prevent unintentional displacement of the graft or extrusion of the graft from the fistula of a patient, the graft may be provided with a cap that extends laterally from at least one end of the body of the graft, where the cap may be integral with the body of the graft, attachable to at least one end of the body of the graft, and/or moveable along the body of the graft. The graft may also have a tail that extends from one end of the body of the graft to assist in placement of the graft in a fistula tract. The graft may be an integral unit made of a single material, such as a heterograft material, or may include distinct components made of the same or different materials. Methods for closing a fistula tract are also provided.

The present invention is a porcine animal, tissue, organ, cells and cell lines, which lack any expression of functional alpha 1,3 galactosyltransferase (alpha1,3GT). These animals, tissues, organs and cells can be used in xenotransplantation and for other medical purposes.

The present technology is related to the field of sterilization and decellularization of allografts or xenografts, specifically to processes that achieve effective removal of the cells contained within a vascular tissue matrix and an effective reduction in potential harmful organisms to create grafts suitable for human implantation. In some embodiments, vascular grafts, vascular tissue and/or blood vessels are contacted with cleaning solution under conditions suitable conditions to reduce immune reaction in patients. More specifically, the present technology is directed to sterilization and decellularization of vascular grafts.

The invention relates to heart valve xenografts from transgenic pigs having a disruption of an α1-3 galactosyl transferase nucleic acid sequence and use of the xenografts for treating a patient.

Development of a physiologically relevant 3D model system for cancer research and drug development represents quite a challenge. We have adopted a 3D culture system based on a transglutaminase-crosslinked gelatin gel (Col-Tgel) to mimic tumor 3D microenvironment. The system has several unique advantages over other alternatives which include cell-matrix interaction sites provided by collagen derived peptides, a 3D construct suitable for reproducing the solid tumor microenvironment including multicellular tumor spheroids and metabolic gradients. In addition the controllable gel stiffness provides a wide range of mechanical restrictions; and compatibility with imaging based screening due to its transparent properties. In addition the Col-Tgel provides a cure-in-situ delivery vehicle for tumor xenograft formation in animals with a high take rate. Overall, this unique 3D system could provide a platform to accurately mimic in vivo situations to study tumor formation and progression both in vitro and in vivo, as well as for screening antineoplastic drugs and assessing the occurrence of drug resistance related to cancer cell stress.

The invention provides an article of manufacture comprising a substantially non-immunogenic heart valve xenograft for implantation into humans. The invention further provides methods for preparing a heart valve xenograft by removing at least a portion of a soft tissue from a non-human animal to provide a xenograft; washing the xenograft in saline and alcohol; subjecting the xenograft to cellular disruption treatment; treating the xenograft with crosslinking agents, and digesting the xenograft with a proteoglycan-depleting factor and/or glycosidase. The invention also provides an article of manufacture produced by the above-identified method of the invention. The invention further provides a heart valve xenograft for implantation into a human including a portion of a heart valve from a non-human animal, wherein the portion has extracellular components and substantially only dead cells. The extracellular components have reduced proteoglycan molecules. Each of the xenografts of the invention are substantially non-immunogenic and have substantially the same mechanical properties as a corresponding native heart valve.

The invention herein described relates to a method to improve the tolerance of a mammal, preferably a human, to a xenograft through immunisation of the recipient mammal with an immunogen comprising both a B cell epitope derived from porcine polypetides and T cell epitope. The invention also encompasses immunogenic compositions comprising said immunogens and methods to monitor the status of the xenograft.

This invention provides a method of generating antigen specific allospecific human-suppressor CD8+CD28− T cells. This invention also provides a method of generating xenospecific human suppressor CD8+CD28− T cells. This invention further provides a method of generating allopeptide antigen specific human suppressor CD8+CD28− T cells. Methods of treatment for, reduction of risk of rejection of allografts and xenografts and autoimmune diseases using the human suppressor CD8+CD28− T cells so produced are also provides, as are methods of preventing rejection and autoimmune diseases, and vaccines comprising the produced suppressor T cells. Methods of diagnosis to determine whether a level of immuno-suppressant therapy requires a reduction are provided.

The present invention is directed to the prophylatic field treatment of photodamaged skin with topical ingenol mebutate. More specifically, the present invention concerns field-directed treatment of UV-damaged skin with topical ingenol mebutate for reducing the number of skin lesions that emerge from the UV-damaged skin over time. In addition, the present invention concerns field-directed treatment for removing photodamaged skin, mutated keratinocytes, cutaneous immunosuppressive environments and/or p53+ patches caused by UV with topical ingenol mebutate. By way of example, the present invention is directed to treating photodamaged skin with topical ingenol mebutate at about 0.05% concentration.

The present invention is also concerned with the treatment of SCC tumors with topical ingenol mebutate for reducing the number of SCC tumors. By example, the present invention is directed to treating and curing SCC xenografts with topical ingenol mebutate at about 0.25% concentration.

The present invention is further directed to a topical field-directed treatment for the removal of tattoos from skin with ingenol mebutate. By way of example, the present invention is directed to removing tattoos with topical ingenol mebutate at concentrations of up to about 0.25%.

The present invention provides human transplantable inflammatory breast carcinoma xenografts. Such xenografts exhibit a number of unique characteristics which allows their use in experimental models of inflammatory carcinoma in order to dissect out the molecular basis of this phenotype. This experimental model of inflammatory carcinoma can be used to identify molecular targets for therapeutic intervention and to assess the efficacy of a broad spectrum of diagnostic and therapeutic agents. Specific animal models of inflammatory breast cancer are described as well as methods for evaluating diagnostic and therapeutic agents for treating inflammatory breast cancer. Methods for identifying molecules whose expression is modulated in inflammatory breast cancer are provided. In addition, methods for diagnosing and inhibiting the growth of inflammatory breast cancer metastases in vivo are provided.

Bioengineering the regenerative heart or other body organ in need of greater muscle mass or improved blood perfusion provides a novel treatment for organ weakness or failure. In the case of cardiac failure treatment, on May 14, 2002, a 55-year-old man suffering ischemic myocardial infarction received 25 injections carrying 465 million cGMP-produced pure myoblasts into his myocardium after coronary artery bypass grafting. Three myogenesis mechanisms were elucidated with 17 human/porcine xenografts using cyclosporine as immunosuppressant. Some myoblasts developed to become cardiomyocytes. Others transferred their nuclei into host cardiomyocytes through natural cell fusion. As yet others formed skeletal myofibers with satellite cells. De novo production of contractile filaments augmented heart contractility. Human myoblasts transduced with VEGF165 gene produced six times more capillaries in porcine myocardium than placebo. Xenograft rejection was not observed for up to 20 weeks despite cyclosporine discontinuation at 6 weeks.

The subject invention pertains to materials, including sets of nerve grafts, for performing breast neurotization with xenograft nerves in breast surgeries, such as reconstructive breast surgery. Certain embodiments of the set of nerve grafts comprise at least two nerve grafts prepared from one or more nerves, such as one or more intercostal nerves (ICNs), obtained from one or more animal sources. Such animal-sourced nerve grafts may be used as xenografts in the reconstruction of nerve defects in humans, and in particular, animal-sourced ICN grafts may be used as xenografts in the reconstruction of ICN nerve defects in humans, including through use of the breast neurotization technique described herein. These animal-sourced nerve grafts may also be used in the reconstruction of nerve defects in animal recipients, including as xenografts, allografts and autografts.

The present invention provides compositions and methods for the prevention and treatment of aggressive immune processes to life-saving grafts, such as xenograft rejection, and for attenuating host responses in transplantation of tissues, cells and organs. More specifically, the compositions and methods of the present invention relate to combined therapies comprising treatment of alpha-1-antitrypsin (AAT) and temporary T-cell depletion including but not limited to anti-CD4 and anti-CD8 antibodies.

An embodiment of the invention is a method of using a xenograft as a control tissue for histology, comprising staining both a patient and a xenograft-derived control sample under substantially similar staining conditions, and assessing the staining outcomes of the two to determine whether the stain was effective for the patient sample. A xenograft has never been used before in histology as a control, as far as the inventors know. The result of using a xenograft as a control is surprisingly advantageous. First, the cell lines grow and differentiate similarly to a human, taking on the general morphology of a real tissue sample. Second, because the same transformed cell line can be grown limitless times in SCID mice, the xenograft control is highly reproducible, leading to a consistent artificial control that is highly manufacturable and subject to genetic manipulation so that antigens or genetic elements may be embedded in the tissue. Another embodiment of the invention is directed generally to a method of making a tissue control substrate, comprising growing a xenograft from a mammalian transformed cell line in a host animal, removing the xenograft from the host animal, processing the xenograft thereby embedding the xenograft tissue in an embedding medium, and finally affixing the embedded xenograft sample onto a substrate. The substrate is generally a microscope slide. The xenograft control slide can then be stained side-by-side with a specimen sample in an automated slide stainer, and act as a control against which the staining quality can be compared. The xenograft control can also be used as a manual staining control. Determining whether the staining was effective for the patient specimen comprises judging the staining intensity of the xenograft control sample to determine if the expected degree and type of staining were realized in the control. If the expected type (nuclear, membranous, or cytoplasmic) and degree (0-4 scale) of staining are realized during the run, then the xenograft control indicates the staining process and reagents are working properly, and so the result in the patient specimen can be trusted. A further embodiment of the invention is a xenograft-derived control slide for histochemical use, comprising at least one xenograft control sample prepared for histological use, and a sample slide upon which the at least one xenograft control sample is affixed.

The invention relates to a method for producing a tissue matrix for an allotransplantation or a xenotransplantation, according to which, once a biological tissue has been obtained, said tissue is classified, said tissue is treated and the tissue matrix produced is conditioned, all of said steps being implemented in an automated manner inside the same 'classified' reactor. The invention also relates to the reactor allowing the implementation of the method of the invention.

The invention provides a construction method of a malignant neurinoma xenograft mouse model. The method comprises the following steps of: resuscitating a tumor tissue block of a malignant neurinoma patient stored in a liquid nitrogen environment; and carrying out xenogeneic subcutaneous transplantation on the resuscitated tumor tissue block of the patient into immunodeficient mouse bodies under asterile condition. The xenogeneic subcutaneous transplantation comprises the following steps: selecting immunodeficient mice with the age of 2-6 weeks, wherein the sex of the mice is kept consistent with that of the patient; soaking the resuscitated tumor tissue block of the patient in sterile incubation liquid containing fetal calf serum; fixing the mice after anesthesia; implanting the tumor tissue block of the patient under the skin of the mice; suturing incision; and raising the mice to enable tumors in the body of the mice to grow. The method also includes: performing xenogeneic orthotopic transplantation on the cryopreserved and resuscitated tumor tissue block of the patient into immunodeficient mice. According to the invention, the xenograft mice are used for replacing clinical patients to screen different combined medicines, so that the most appropriate medicine is selected, the effectiveness is greatly improved, and the side effects of the medicines are reduced.

The present invention provides a method of modifying or engineering cells that are intended for introduction into a host as a xenograft, the modification or engineering of the cells comprising inclusion of at least one suitable reporter system. Inclusion of a reporter system permits monitoring of the xenograft and determination of xenograft parameters of interest through appropriate and convenient measurement systems.

IDH1 gene-defective cell lines (e.g., IDH1R132H heterozygous) have been made from a robust cell line, HCT116. The IDH1 gene-defective cell lines can be used to determine the effect of IDH1R132H on cell biology, tumorigenesis, and cellular metabolic profiles. These cell lines can be used to test potential therapeutic targets and to screen potential therapeutic agents. Kits and xenografts are also contemplated.