Abstract:
This invention relates to immunogenic luteinizing hormone releasing hormone (LHRH) peptides that lead to suppression of LHRH activity in males or females. These peptides are useful for inducing infertility and for treating prostatic hyperplasia, androgen-dependent carcinoma, prostatic carcinoma and testicular carcinoma in males. In females, the peptides are useful for treating endometriosis, benign uterine tumors, recurrent functional ovarian cysts and (severe) premenstrual syndrome as well as prevention or treatment of estrogen-dependent breast cancer. The subject peptides contain a helper T cell epitope and have LHRH at the C terminus. The helper T cell epitope aids in stimulating the immune response against LHRH. The peptides, optionally contain an invasin domain which acts as a general immune stimulator. In another aspect this invention relates to immunogenic synthetic peptides having an invasin domain, a helper T cell epitope and a peptide hapten and methods of using these peptides to treat disease or provide protective immunity. The peptide haptens of the invention include LHRH, amylin, gastrin, gastrin releasing peptide, IgE CH4 peptide, Chlamydia MOMP peptides, HIV V3 peptides and Plasmodium berghei.
Abstract:
A chimeric toxin comprising protein fragments joined together by peptide bonds, the chimeric toxin comprising, in sequential order, beginning at the amino terminal end of the chimeric toxin, (a) the enzymatically active Fragment A of diphtheria toxin, (b) a first fragment including the cleavage domain 1.sub.1 adjacent the Fragment A of diphtheria toxin, (c) a second fragment comprising at least a portion of the hydrophobic transmembrane region of Fragment B of diphtheria toxin, the second fragment having a deletion of at least 50 diphtheria toxin amino acid residues, the deletion being C-terminal to the portion of the transmembrane region, and the second fragment not including domain 1.sub.2, and (d) a third fragment comprising a portion of a cell-specific polypeptide ligand, the portion including at least a portion of the binding domain of the polypeptide ligand, the portion of the binding domain being effective to cause the chimeric toxin to bind selectively to a predetermined class of cells to be attacked by the enzymatically active Fragment A, the chimeric toxin possessing any of, greater toxicity than that of a toxin comprised of DAB.sub.486 fused to the third fragment, a lower K.sub.d for the sites on cells of the predetermined class to which the chimeric toxin binds than that of a toxin comprised of DAB.sub.486 fused to the third fragment, greater resistance to proteolytic degradation than that exhibited by a toxin comprised of DAB.sub.486 fused to the third fragment, greater resistance to the inhibition of its cytotoxicity by the cell-specific polypeptide ligand than that exhibited by DAB.sub.486 fused to the third fragment, the ability to inhibit protein synthesis to a given degree by a period of exposure that is shorter than the period of exposure required by DAB.sub.489 fused to the third fragment to inhibit protein synthesis to the same degree, or the ability to effect a more rapid onset of the inhibition of protein synthesis than that exhibited by DAB.sub.486 fused to the third fragment.
Abstract:
All lines of mammalian origin which have been stably transformed with a chimeric toxin gene expressed under the regulatory control of HIV cis-acting sequences and HIV trans-acting factors are provided by the present invention. HIV infection of a cell of such a transformed cell line results in the death of that cell due to the specific induction of toxin gene expression within the cell. As specifically exemplified, the toxin gene is the diphtheria toxin fragment A gene or a tox176 fragment A chain gene. Also provided by the present invention are recombinant nucleic acid molecules suitable for the stable transformation of a mammalian cell line to produce a transformed cell which will effectively commit suicide in response to HIV infection due to induction of toxin gene expression.
Abstract:
A potent and specific immunotoxin is prepared by coupling a binding-site inactivated diphtheria toxin (CRM 107) to a new binding moiety consisting of transferrin or a monoclonal antibody against the human transferrin receptor. These immunotoxins are tumor specific and lack the nonspecific toxicity produced by the binding activity of the native toxin. The immunotoxin is useful in treating primary brain tumors, metastatic tumors to the brain, CSF-borne tumors, leptomeningeal leukemia and leptomeningeal carcinomatosis.
Abstract:
A new thiolated polypeptide compound derived from a fragment of tetanus toxin, the process for its obtention and its applications.This compound consists of the II.sub.c fragment of tetanus toxin, having at least one --SH group either directly or indirectly bound thereto. It is usable as a specific neuropharmacological transport agent for transporting a medicine to the central nervous system, as a specific labelling agent for neuronal cells or for diagnosis purposes. It can be coupled with a medicine or a labelling agent.
Abstract:
The present invention provides methods for inhibiting interleukin-3 receptor-expressing cells, and, in particular, inhibiting the growth of such cells by using a diphtheria toxin-human interleukin-3 conjugate (DT-IL3) that is toxic to cells expressing the interleukin-3 receptor. In preferred embodiments, the DT-IL3 conjugate is a fusion protein comprising amino acids 1-388 of diphtheria toxin fused via a peptide linker to full-length, human interleukin-3. In certain embodiments, the methods of the present invention relate to the administration of a DT-IL3 conjugate to inhibit the growth of cancer cells and/or cancer stem cells in humans, which cells express one or more subunits of the interleukin-3 receptor. Exemplary cells include myeloid leukemia cancer stem cells. In other embodiments, the methods of the present invention relate to ex vivo purging of bone marrow or peripheral blood to remove cells that express one or more subunits of the interleukin-3 receptor such that the purged bone marrow or peripheral blood is suitable, e.g., for autologous stem cell transplantation to restore hematopoietic function.
Abstract:
The present invention is directed to the cells, compositions and methods for the production of recombinant protein, wherein an f-met group on the 5′-terminus is enzymatically removed. In particular, the invention is directed to a production process for obtaining high levels of soluble recombinant CRM197 protein from E. coli. Cells preferably contain one or more mutations of disulfide reductase genes, so that disulfide reductase activity is reduced. The invention also relates to purification method for CRM197 as well as characterization of properly folded CRM197 protein.
Abstract:
Disclosed are polypeptides comprising a diphtheria toxin and a PD1 targeting moiety. Disclosed are polypeptides comprising, from N- to C-terminus, a truncated diphtheria toxin, and two anti-PD-1 scFvs. Disclosed are nucleic acid constructs comprising a nucleic acid sequence encoding any one of the disclosed polypeptides. Disclosed are nucleic acid constructs comprising a nucleic acid sequence encoding a diphtheria toxin linked to a nucleic acid sequence encoding a PD1 targeting moiety. Disclosed are methods of treating a subject in need thereof comprising administering to the subject a composition comprising one or more of the disclosed polypeptides, vectors, or pharmaceutical compositions.
Abstract:
The present disclosure is generally directed to an anucleated cell-based platforms for encapsulation and delivery of agricultural compounds. Disclosed herein are compositions for the stable and targeted delivery of agricultural compounds within achromosomal and/or anucleated cells. The present disclosure also provides methods of improving encapsulation and retention of agricultural compounds in achromosomal and/or anucleated cells.
Abstract:
Methods for the production of immunogenic compositions containing a non-natural amino acid are disclosed. The non-natural amino acid can be a site for attachment of antigens, such as bacterial capsular polysaccharides, to make immunogenic conjugates. Bio-orthogonal attachment chemistry incorporated into the non-natural amino acids allows for more efficient and potent antigen presentation to the immune system, simplified purification, and more well-defined structure of these semi-synthetic immunogens.