Genetically engineered glutaminase and its use in antiviral and anticancer therapy
AssigneesME Medical Enzymes AG, Joseph Roberts
InventorsJoseph Roberts, Thomas W. MacAllister, Natarajan Sethuraman, Abbie G. Freeman
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Abstract
DNA encoding a therapeutically suitable glutaminase has been molecularly cloned. This allows one to obtain a polypeptide which is a therapeutically suitable glutaminase free of contaminating endotoxin. It has been found that this polypeptide is a potent anti-viral agent and when coupled to an anti-tumor monoclonal antibody is a potent anticancer agent. The glutaminase of the present invention is particularly useful for treating lung, breast and colon cancer cells and in the treatment of HIV-infected cells.
Claims46
A method of inhibiting the replication of HIV in HIV-infected cells, comprising:
- administering a therapeutically suitable glutaminase to HIV-infected cells in an amount sufficient to inhibit replication of HIV in said cells.
A method of inhibiting the growth of cancer cells comprising:
- administering a bound complex of a therapeutically suitable glutaminase and an antibody immunoreactive with a tumor-associated antigen to tumor cells which express said tumor associated antigen, the amount of said complex administered being sufficient to inhibit DNA synthesis in said cells.
An E. coli cell which comprises Pseudomonas 7A glutaminase-asparaginase gene.
An isolated and purified DNA molecule comprising a nucleotide sequence coding for a therapeutically suitable glutaminase.
A cell-free preparation of a therapeutically suitable glutaminase which is free of Pseudomonas endotoxin.
A method of treating transformed cells in a body, comprising:
- administering a plasmid comprising the nucleotide sequence of SEQ ID NO:1, said sequence under the transcriptional control of a tissue-specific promoter, said plasmid coated with poly-L-lysine covalently linked to a tissue-specific ligand.
A therapeutic composition comprising:
- a complex comprising a therapeutically suitable glutaminase and an antibody which is specific for a tumour-associated antibody.
A method of treating transformed cells in a body, comprising:
- administering a plasmid comprising the nucleotide sequence of SEQ ID NO:
- 1, said sequence under the transcriptional control of a tissue-specific promoter, said plasmid encapsulated by a cationic liposome which comprises a tissue-specific ligand.
A method of treating a tumour-bearing patient, comprising the steps of:
- obtaining tumour infiltrating lymphocytes from a tumour-bearing patient;
- transfecting said tumour infiltrating lymphocytes with a vector which causes expression of Pseudomonas 7A glutaminase in human cells;
- administering said transfected tumour infiltrating lymphocytes to the patient to supply said tumour with Pseudomonas 7a glutaminase.
A method of treating a tumour-bearing patient, comprising the steps of:
- obtaining tumour infiltrating lymphocytes from a tumour-bearing patient;
- complexing said tumour infiltrating lymphocytes with a vector comprising the nucleotide sequence of SEQ ID NO:
- 1, said vector causing expression of Pseudomonas 7A glutaminase in human cells;
- administering said complex of lymphocytes and vector to the tumour-bearing patient to supply said tumour with Pseudomonas 7A glutaminase.
Dependencies are inferred from the claim text.