Nk cells activiating receptors and their therapeutic and diagnostic uses
OwnerOfer Mandelboim, Angel Porgadorinventors
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Abstract
The invention relates to a targeting complex, capable of targeting an active substance to a target cell, said complex comprising: a target recognition segment comprising one of NKp46, NKp30, NKp44 or a functional fragment thereof; and an active segment comprising an active substance such as cytotoxic moiety; an imaging moiety; or an Ig fragment. The targeting complex of the invention serves as a therapeutic agents for the treatment of pathologies associated with viral infections or cancer and for the imaging and monitoring of cancer.
Claims82
A targeting complex, capable of targeting an active substance to a target cell, said complex comprising:
- a. a target recognition segment comprising one of NKp46, NKp30, NKp44 or a functional fragment thereof;
- and
- b. an active segment comprising said active substance, said active substance being selected from the group consisting of:
- a cytotoxic moiety;
- an imaging moiety;
- and
- an Ig fragment.
An expression vector comprising a DNA coding for a NKp46-Ig fusion protein, said protein comprising:
- a. a target recognition segment which comprises NKp46 or functional fragments thereof;
- and
- b. an active segment which is the Fc portion of an Ig molecule.
An expression vector comprising a DNA coding for a NKp44-Ig fusion protein said protein comprising:
- a. a target recognition segment which comprises NKp44 or functional fragments thereof;
- and
- b. an active segment which is the Fc portion of an Ig molecule.
A NKp46-Ig fusion protein comprising the amino acid sequence substantially as denoted by any one of SEQ ID NO:
- 6, SEQ ID NO:
- 14, encoded by the nucleic acid sequence substantially as denoted by SEQ ID NO:
- 3 and SEQ ID NO:
- 12, respectively.
A NKp44-Ig fusion protein comprising the amino acid sequence substantially as denoted by SEQ ID NO:
- 10, encoded by the nucleic acid sequence substantially as denoted by SEQ ID NO:
- 8.
An antibody that specifically recognizes and binds to an epitope on a protein, wherein said protein is a ligand for any one of the NK cell activating receptor NKp46 and NKp44.
A composition for the treatment of a pathological condition comprising as active ingredient a complex comprising:
- a. a target recognition segment capable of specifically recognizing and binding to a diseased target cell involved with said pathological condition, said recognition segment comprising one of NKp46, NKp44, NKp30 or a biologically functional fragment thereof;
- and
- b. an active segment selected from the group consisting of a cytotoxic moiety and an Ig fragment.
A diagnostic composition for detecting the presence of diseased cells in a sample comprising a complex comprising:
- a. a target recognition segment capable of specifically recognizing and binding to a diseased target cell involved with said pathological condition, said recognition segment comprising one of NKp46, NKp44, NKp30 or a biologically functional fragment thereof;
- and
- b. a detectable imaging segment which is an imaging moiety selected from the group consisting of paramagnetic, radioactive and fluorogenic agent.
A method for treating a pathological condition in a subject comprising administering to the subject a therapeutically effective amount of a complex or pharmaceutical agent comprising the same, said complex comprising:
- a. a first target recognition segment capable of specifically recognizing and binding to a diseased target cell involved with said pathological condition, said recognition segment comprising one of NKp46, NKp44, NKp30 or a biologically functional fragment thereof;
- and
- b. an active segment selected from the group consisting of a cytotoxic moiety and an Ig fragment.
A method for the diagnosis and imaging of malignant cells in a subject comprising the steps of introducing an imaging agent into the blood-stream of said subject, and detecting and quantitating the binding of said imaging agent to any one of NKp46, NKp30 and NKp44 ligands expressed on target malignant cells, wherein said imaging agent comprises a complex having:
- a. a first target recognition segment, capable of specifically recognizing and binding to said malignant cells, said recognition segment comprising one of NKp46, NKp30, NKp44 or a biologically functional fragment thereof;
- and
- b. an active segment which is an imaging moiety, said imaging moiety being selected from the group consisting of paramagnetic, radioactive and fluorogenic agents.
Dependencies are inferred from the claim text.