Abstract: A single-chain immunotoxin composition and method of treatment with the composition is disclosed. Preferably, the immunotoxin is comprised of a CD33-specific single chain Fv antibody fragment and a genetically engineered variant of Pseudomonas Exotoxin A (ETA). A preferred engineered Exotoxin A is referred to ETA? and may includes a KDEL peptide at its C-terminus, a cellular peptide mediating improved retrograde transport to the endoplasmic reticulum (ER). The immunotoxin compound may be formulated with a carrier and administered into patients where the antibody portion binds to CD33-positive cells and kills those cells to provide an effective treatment for diseases such as human myeloid leukemia.

Abstract: Provided is an immunotoxin including (a) an anti-CD19 antibody lacking an Fc fragment, (b) a modified exotoxin A protein having both Domains II and III, but lacking Domain I, and (c) a peptide linker joining the C-terminal end of the antibody to the N-terminal end of the modified exotoxin A protein. The linker is substantially resistant to extracellular cleavage. The modified exotoxin A protein may be further modified to include a C-terminal KDEL sequence (SEQ ID NO: 6) that promotes transport of the protein to the endoplasmic reticulum of cells that have taken up the immunotoxin. Also provided is an anti-CD19 antibody having enhanced binding activity, antibody-dependent cellular cytotoxicity (ADCC) and methods for using the antibody to treat a disease state associated with B-lineage cells that express CD19. The antibody variable light and variable heavy chains have unique sequences in their J region relative to known anti-CD19 antibody sequences.

Abstract: A method and kit for inhibiting the proliferation of cancer cells are disclosed, based on a combination of an apoptosis-inducing immunologic agent, and a sensitizing agent. When used in cancer therapy, the two agents in combination enhance the anti-cancer treatment efficacy obtained with the immunologic agent or the sensitizing agent alone, by a supraadditive amount.

Abstract: An immunotoxin for use in, and a method for treating a subject having a cancer associated with malignant B-lineage cells or an autoimmune condition, are disclosed. The immunotoxin includes (a) an anti-CD19 antibody lacking an Fc fragment, (b) a modified exotoxin A protein having both Domains II and III, but lacking Domain I, and (c) a peptide linker joining the C-terminal end of the antibody to the N-terminal end of the modified exotoxin A protein. The linker is substantially resistant to extracellular cleavage. The modified exotoxin A protein may be further modified to include a C-terminal KDEL sequence (SEQ ID NO: 6) that promotes transport of the protein to the endoplasmic reticulum of cells that have taken up the immunotoxin.