Trispecific therapeutics against acute myeloid leukaemia

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

This patent describes a novel trispecific therapeutic molecule intentionally engineered to bind three specific targets: CD123, CD16, and CD33. The molecule is constructed by linking three immunoglobulin variable domains—each specifically binding to one of the three targets—into a single chain, often stabilized with disulfide bonds. This structure allows the molecule to target acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) cells that express CD123 and/or CD33, while simultaneously engaging immune effector cells (such as natural killer cells via CD16) to promote efficient tumor cell destruction through antibody-dependent cellular cytotoxicity (ADCC). The invention can be used both as a protein therapeutic and at the nucleic acid/vector level for production or gene therapy purposes.

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

• Targeted treatment of acute myeloid leukemia (AML) by eliminating leukemia stem cells that express CD123 and/or CD33.
• Potential treatment for myelodysplastic syndrome (MDS), particularly targeting disease-propagating cells during or after remission.
• Development of diagnostic assays to detect AML/MDS cells via their expression of CD123 and CD33.
• Therapeutic intervention during minimal residual disease (MRD) phase post-chemotherapy to prevent relapse in AML patients.
• Possible use as a platform for other multispecific cancer immunotherapies by varying target antigens.

BenefitsContent extracted from patent full text and abstract with AI.

• Enhanced specificity: Simultaneous binding to two tumor-associated antigens (CD123 and CD33) increases tumor cell targeting accuracy, reducing off-target effects compared to monospecific or bispecific therapeutics.
• Efficient immune activation: The CD16-binding domain recruits natural killer (NK) cells and monocytes/macrophages, providing potent antibody-dependent cellular cytotoxicity (ADCC) for tumor cell elimination.
• Reduction of relapse: Direct targeting and removal of leukemia stem cells implicated in disease relapse, addressing a major limitation of standard chemotherapy.
• Lower toxicity: Unlike chemotherapeutics or immunotoxins, the trispecific molecule does not involve conjugated chemical or plant toxins, potentially offering a better safety profile.
• Stability and manufacturability: Engineered disulfide bonds and modular single-chain format increase molecular stability, simplify production, and may improve pharmacokinetics.
• Diagnostic utility: The molecule’s high specificity and affinity also make it suitable for sensitive detection of AML/MDS cells in diagnostic applications.

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Patent Abstract

The present invention relates to a molecule having binding specificities for (a) CD123; (b) CD16 and (c) CD33. The present invention further relates to the molecule of the invention, wherein the molecule comprises a first immunoglobulin domain comprising a V L domain linked to a V H domain, wherein the immunoglobulin domain specifically binds to CD123; a second immunoglobulin domain comprising a V L domain linked to a V H domain, wherein the immunoglobulin domain specifically binds to CD16; and a third immunoglobulin domain comprising a V L domain linked to a V H domain, wherein the immunoglobulin domain specifically binds to CD33. The present invention furthermore relates to a nucleic acid molecule encoding the molecule of the invention. In addition, the present invention relates to diagnostic and pharmaceutical compositions and the use of the molecule or the nucleic acid molecule of the invention in the treatment of acute myeloid leukaemia and/or myelodysplastic syndrome.