The present disclosure relates to pharmaceutical compositions comprising a non-naturally occurring fusion molecule and one or more pharmaceutically acceptable carriers, formulated for oral delivery to a subject, and designed to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases, autoimmune diseases, cancer, metabolic disorders, and growth deficiency disorders. The present disclosure relates to a non-toxic mutant form of the Vibrio cholera Cholix gene (ntCholix), a variant of Cholix truncated at amino acid A.sup.386 (Cholix.sup.386) and the use of other various Cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. The systems and methods described herein provide for: the ability to deliver macromolecule doses without injections; the ability to deliver cargo such as siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes.

A ligand recombinant protein inhibiting HB-EGF (Heparin-Binding Epidermal Growth Factor like), from the R domain of diphtheria toxin, which can be used for the treatment and diagnosis of diseases involving the activation of the HB-EGF/EGFR pathway.

The present disclosure relates to pharmaceutical compositions comprising a non-naturally occurring fusion molecule and one or more pharmaceutically acceptable carriers, formulated for oral delivery to a subject, and designed to provide for improved, effective therapies for treatment of, e.g., inflammatory diseases, autoimmune diseases, cancer, metabolic disorders, and growth deficiency disorders. The present disclosure relates to a non-toxic mutant form of the Vibrio cholera Cholix gene (ntCholix), a variant of Cholix truncated at amino acid A.sup.386 (Cholix.sup.386) and the use of other various Cholix-derived polypeptide sequences to enhance intestinal delivery of biologically-active therapeutics. The systems and methods described herein provide for: the ability to deliver macromolecule doses without injections; the ability to deliver cargo such as siRNA or antisense molecules into intracellular compartments where their activity is required; and the delivery of nanoparticles and dendrimer-based carriers across biological membranes.

The present invention provides compounds, compositions, and methods for detecting, diagnosing and treating cancers such as glioblastoma multiforme.

This disclosure provides a bispecific ligand directed toxin (BLT) that includes a diphtheria toxin (DT) molecule that has been mutated to create a DT molecule that induces less of an immune response than native diphtheria toxin. The deimmunized DT molecule is fused with targeting ligands to create a fusion protein that can selectively deliver the deimmunized DT to target cells to kill the target cells.

Provided herein are HER2-targeting molecules comprising Shiga toxin A Subunit derived polypeptides having 1) de-immunization and 2) reduced, protease-cleavage sensitivity while retaining Shiga toxin function(s), such as, e.g., potent cytotoxicity via ribosome inhibition. Certain HER2-targeting molecules of the present invention exhibit reduced immunogenic potential in mammals and are well-tolerated by mammals while retaining aforementioned features. The HER2-targeting molecules of the present invention have uses for selectively killing specific cells (e.g., HER positive tumor cells); for selectively delivering cargos to specific cells (e.g., HER positive tumor cells), and as therapeutic and/or diagnostic molecules for treating and diagnosing a variety of conditions, including cancers and tumors involving the expression or over-expression of cell-surface HER2.

The present invention provides, among other things, improved therapeutic compositions comprising a C3 fusion protein and methods of making and using the same. In particular, the present invention provides improved methods for the treatment of spinal cord injury and other CNS trauma and/or facilitate axon growth or other tissue repair.

The present invention is directed to T-cell epitope delivering polypeptides which deliver one or more CD8+ T-cell epitopes to the MHC class I presentation pathway of a cell, including toxin-derived polypeptides which comprise embedded T-cell epitopes and are de-immunized. The present invention provides cell-targeted, CD8+ T-cell epitope delivering molecules for the targeted delivery of cytotoxicity to certain cells, e.g., infected or malignant cells, for the targeted killing of specific cell types, and the treatment of a variety of diseases, disorders, and conditions, including cancers, immune disorders, and microbial infections. The present invention also provides methods of generating polypeptides capable of delivering one or more heterologous T-cell epitopes to the MHC class I presentation pathway, including polypeptides which are 1) B-cell and/or CD4+ T-cell de-immunized, 2) comprise embedded T-cell epitopes, and/or 3) comprises toxin effectors which retain toxin functions.

The present invention is related to a method of treating or preventing cancer in a subject comprising administering to a subject having cancer or prone of getting cancer a first agent that depletes the subject's regulatory T cells (Tregs); followed by administering to the subject a second agent comprising a checkpoint inhibitor.

The present disclosure provides, in part, a method of treating an autoimmune disease in a subject by reducing the number of pDCs through administration of a human interleukin-3 (IL-3)-diphtheria toxin conjugate (DT-IL3). The disclosure also generally relates to methods of monitoring the effectiveness of therapy in subjects receiving DT-IL3 for treating an autoimmune disease, and methods of determining continuing treatment of subjects receiving DT-IL3 for treating an autoimmune disease. The disclosure also provides pharmaceutical compositions of DT-IL3 for use in such methods.