Abstract: This invention provides improved devices and methods for long-term, stable expression of a biologically active molecule using a biocompatible capsule containing genetically engineered cells for the effective delivery of biologically active molecules to effect or enhance a biological function within a mammalian host. The novel capsules of this invention are biocompatible and are easily retrievable. This invention specifically provides improved methods and compositions which utilize cells transfected with recombinant DNA molecules comprising DNA sequences coding for biologically active molecules operatively linked to promoters that are not subject to down regulation in vivo upon implantation into a mammalian host. Furthermore, the methods of this invention allow for the long-term, stable and efficacious delivery of biologically active molecules from living cells to specific sites within a given mammal.

Abstract: The present invention provides an altered antibody molecule (AAM) having a hinge region which has a different number of cysteine residues from that found in the hinge region normally associated with the CH1 domain of the antibody molecule and a process for producing the same using recombinant DNA technology.

Abstract: Stable polyligands are provided by preparing fused proteins, where the fused protein comprises a ligand at one terminus and a subunit of a multimeric unit protein at the other terminus, where the fused protein is able to assemble to provide a polyligand. The polyligands find use in modulating physiological processes by inhibiting ligand induced signal transduction by surface membrane protein receptors and/or in the case of .mu. chain use, by complement mediated killing or any other effector functions. The molecule may be composed solely, of human components to avoid an immune response by the recipient.

Abstract: The present invention provides a non-mouse pluripotential embryonic stem cell which can be maintained on feeder layers for at least 20 passages and give rise to embryoid bodies and multiple differentiated cell phenotypes in monolayer culture. The invention further provides a method of making a pluripotential embryonic stem cell comprising administering a growth enhancing amount of basic fibroblast growth factor, leukemia inhibitory factor, membrane associated steel factor, and soluble steel factor to primordial germ cells under cell growth conditions, thereby making a pluripotential embryonic stem cell.

Abstract: Methods, including culture media conditions, which provide for ex vivo human stem cell division and/or the optimization of human hematopoietic progenitor cell cultures and/or increasing the metabolism or GM-CSF secretion or IL-6 secretion of human stromal cells are disclosed. The methods rely on culturing human stem cells and/or human hematopoietic progenitor cells and/or human stromal cells in a liquid culture medium which is replaced, preferably perfused, either continuously or periodically, at a rate of 1 ml of medium per ml of culture per about 24 to about 48 hour period, and removing metabolic products and replenishing depleted nutrients while maintaining the culture under physiologically acceptable conditions. Optionally growth factors are added to the culture medium.

Abstract: Methods, including culture media conditions, which provide for ex vivo human stem cell division and stable genetic transformation and/or the optimization of human hematopoietic progenitor cell cultures and/or increasing the metabolism or GM-CSF secretion or IL-6 secretion of human stromal cells are disclosed. The methods rely on culturing human stem cells and/or human hematopoietic progenitor cells and/or human stromal cells in a liquid culture medium which is replaced, preferably perfused, either continuously or periodically, at a rate of 1 ml of medium per ml of culture per about 24 to about 48 hour period, and removing metabolic products and replenishing depleted nutrients while maintaining the culture under physiologically acceptable conditions. Optionally growth factors are added to the culture medium.

Abstract: Novel regimens are provided for administering foreign genetically modified allogeneic cells to a host by combining the administration of the cells with a reduced regimen of an immunosuppressive agent. Particularly, cells having a reduced level of Class I MHC antigens may be employed in a variety of cellular therapy situations, where foreign cells are engrafted to treat diseased states.

Abstract: The human tumor-associated antigen CO-029 is a monoclonal antibody-defined, 27-34 kDa cell surface glycoprotein. A full-length cDNA clone for CO-029 is described. When transiently expressed in COS cells, the cDNA clone directs the synthesis of an antigen reactive with monoclonal antibody CO-029 in mixed hemadsorption and immunoblot assays. Sequence analysis reveals that CO-029 belongs to a family of cell surface antigens which includes the melanoma-associated antigen ME491, the leukocyte cell surface antigen CD37, and the Sm23 antigen of the parasitic helminth Schistosoma mansoni.

Abstract: A unique gene sequence encoding a natural killer lytic associated molecule (natural killerlytic associated protein) has been isolated. Using recombinant DNA techniques, the natural killerlyric associated protein may be produced in useful quantities. Methods for preparing the gene sequence and the gene product are disclosed, as well as methods of using the product to enhance anti-tumor, anti-viral and anti-microbial activity of natural killer cells. A method of inhibiting expression of the gene product is also disclosed, which may be used to turn off immune responses in situations of graft rejection and autoimmune disorders. Furthermore, methods of treating tumors and viruses in humans have been developed.

Abstract: The present invention relates to a non-human chimeric mammal having characteristics of a functional human immune system and having functional human lymphocytes reconstituted in the mammal's lymphopoietic tissue, particularly the spleen. The invention also relates to a method of preparing a non-human chimeric mammal, having characteristics of a functional human immune system, by engraftment of human peripheral blood leukocytes into an immunocompromised mammal. Use of the chimeric mammal as a model of the human immune system is described.

Abstract: The invention relates to transgenic non-human animals capable of producing heterologous antibodies and transgenic non-human animals having inactivated endogenous immunoglobulin genes. In one aspect of the invention, endogenous immunoglobulin genes are suppressed by antisense polynucleotides and/or by antiserum directed against endogenous immunoglobulins. Heterologous antibodies are encoded by immunoglobulin genes not normally found in the genome of that species of non-human animal. In one aspect of the invention, one or more transgenes containing sequences of unrearranged heterologous human immunoglobulin heavy chains are introduced into a non-human animal thereby forming a transgenic animal capable of functionally rearranging transgenic immunoglobulin sequences and producing a repertoire of antibodies of various isotypes encoded by human immunoglobulin genes. Such heterologous human antibodies are produced in B-cells which are thereafter immortalized, e.g.

Abstract: The invention provides expression vectors containing the promoter, enhancer and substantially complete 5'-untranslated region including the first intron of the major immediate early gene of human cytomegalovirus. Further vectors including the hCMV-MIE DNA linked directly to the coding sequence of a heterologous gene are described. Host cells transfected with the vectors and a process for producing heterologous polypeptides using the vectors and the use of the hCMV-MIE DNA for expression of a heterologous gene are also included within the invention.

Abstract: The invention features methods of replacing thymus function and inducing immunological tolerance.

Abstract: This invention provides improved devices and methods for long-term, stable expression of a biologically active molecule using a biocompatible capsule containing genetically engineered cells for the effective delivery of biologically active molecules to effect or enhance a biological function within a mammalian host. The novel capsules of this invention are biocompatible and are easily retrievable. This invention specifically provides improved methods and compositions which utilize cells transfected with recombinant DNA molecules comprising DNA sequences coding for biologically active molecules operatively linked to promoters that are not subject to down regulation in vivo upon implantation into a mammalian host. Furthermore, the methods of this invention allow for the long-term, stable and efficacious delivery of biologically active molecules from living cells to specific sites within a given mammal.

Abstract: We have discovered that using non-integrative viral vectors having low replicative efficiency for insertion of a gene into a cell such as a lymphocyte or a tumor cell is a preferred system for transforming such cells for use in somatic cell therapy or gene therapy. These vectors are preferably cytoplasmic viral vectors, as opposed to nuclear viral vectors. Preferred cytoplasmic vectors include DNA viruses such as pox viruses and iridoviruses and RNA viruses such as picornavirus, calicivirus and togavirus. More preferably the virus used will not be capable of sustained replication in the target cell. For example, a preferred pox virus for human cells will be an avipox, or suipox in contrast to an orthopox virus such as vaccinia.

Abstract: This invention provides improved devices and methods for long-term, stable expression of a biologically active molecule using a biocompatible capsule containing genetically engineered cells for the effective delivery of biologically active molecules to effect or enhance a biological function within a mammalian host. The novel capsules of this invention are biocompatible and are easily retrievable. This invention specifically provides improved methods and compositions which utilize cells transfected with recombinant DNA molecules comprising DNA sequences coding for biologically active molecules operatively linked to promoters that are not subject to down regulation in vivo upon implantation into a mammalian host. Furthermore, the methods of this invention allow for the long-term, stable and efficacious delivery of biologically active molecules from living cells to specific sites within a given mammal.

Abstract: A method of producing foreign gene products which comprises (1) transforming animal cells either (a) by using two plasmids, namely a plasmid containing the MMTV LTR and a foreign gene encoding a physiologically active substance inserted therein downstream from the LTR and a plasmid containing the LTR and a glucocorticoid receptor protein gene inserted therein downstream from the LTR, or (b) by using one plasmid comprising the LTR, a glucocorticoid receptor protein gene located downstream from the LTR, another LTR and a foreign gene encoding a physiologically active substance located downstream from the latter LTR, and (2) cultivating the transformed animal cells in a medium containing glucocorticoid in an amount effective for inducing mRNA transcription.

Abstract: Methods, including culture media conditions, which provide for ex vivo human stem cell division and/or the optimization of human hematopoietic progenitor cell cultures and/or increasing the metabolism or GM-CSF secretion or IL-6 secretion of human stromal cells are disclosed. The methods rely on culturing human stem cells and/or human hematopoietic progenitor cells and/or human stromal cells in a liquid culture medium which is replaced, preferably perfused, either continuously or periodically, at a rate of 1 ml of medium per ml of culture per about 24 to about 48 hour period, and removing metabolic products and replenishing depleted nutrients while maintaining the culture under physiologically acceptable conditions. Optionally growth factors are added to the culture medium.

Abstract: The present invention provides mice which are deficient in the normal expression of one or more MHC class II genes, to mice heterozygous for such deficiency, and to cell lines, preferably pluripotent or totipotent cell lines, which are heterozygous, homozygous or chimeric for such deficiency, as well as to the use of any of the above, especially in situations where the absence of at least one MHC gene, or the normal expression thereof, is desirable.

Abstract: Process for the production of proteins with antibody activity in which one or several DNA sequences coding for this protein are introduced into the male pronucleus of a fertilized ovum of a pig or rabbit by microinjection, the ova are implanted in the oviduct of a pig or rabbit, the offspring are bred and the protein with antibody activity is isolated from their serum in the usual way whereby the DNA sequences used for the microinjection are free of bacterial foreign sequences, and are preferably used with immunoglobulin promoter and enhancer sequences.