CD33-specific single-chain immunotoxin and method of use

Simple SummaryContent extracted from patent full text and abstract with AI.

The invention is a CD33-specific single-chain immunotoxin, which is a fusion protein that combines a single-chain antibody fragment (scFv) targeting CD33 (a cell surface antigen commonly found on acute myeloid leukemia cells) with a truncated and genetically modified version of Pseudomonas Exotoxin A (ETA). The toxin is engineered to be delivered specifically into CD33-positive cells, where it induces cell death (apoptosis). The immunotoxin is designed to offer a highly specific therapy for diseases with CD33-positive cells, particularly acute myeloid leukemia (AML) and some forms of acute lymphoblastic leukemia (ALL), reducing off-target effects and toxicity compared to existing treatments.

Use CasesContent extracted from patent full text and abstract with AI.

• Treatment of acute myeloid leukemia (AML), particularly in patients who are relapsed or refractory to standard therapies.
• Treatment of pediatric acute lymphoblastic leukemia (ALL) where the malignant cells express CD33.
• Development of targeted therapies against other cancers or diseases characterized by CD33-positive cells.
• Use as a research tool for selectively depleting CD33-positive cells in cell culture or animal models to study disease mechanisms.
• Potential adaptation for other surface antigens to create targeted immunotoxins for different diseases.

BenefitsContent extracted from patent full text and abstract with AI.

• Highly specific targeting kills only CD33-positive cells, sparing healthy tissue and reducing off-target toxicity.
• Improved safety compared to existing therapies (e.g., Mylotarg) due to stable peptide bond linkage and absence of an Fc region, minimizing unwanted immune reactions and antigen-independent toxicity.
• Engineered toxin (ETA') lacks native mammalian cell binding domains, reducing the risk of toxicity to non-target cells if released extracellularly.
• Effective at low concentrations (nanomolar range), enabling potent activity with small doses.
• Recombinant production in bacteria enables scalable and cost-effective manufacturing.
• Reduced immunogenicity and improved biodistribution due to single-chain, small-sized fusion protein design.

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Inventors & Applicants

Patent 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.