Thymidylate Kinase Mutants and Uses Thereof
OwnerJeffrey A. Medin, Arnon Lavie +1inventors
InventorsJeffrey A. Medin, Arnon Lavie, Daniel H. Fowler
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Abstract
The invention relates to a composition comprising a stably integrating delivery vector; and a modified mammalian thymidylate kinase (tmpk) wherein the modified mammalian tmpk increases phosphorylation of a prodrug relative to phosphorylation of the prodrug by wild-type human tmpk. The invention also relates to use of these compositions in methods of treatment of diseases such as graft versus host disease and cancer.
Claims24
A method of providing a cell transplant recipient with an actuable cell transplant safety component comprising:
- a) expressing a modified mammalian thymidylate monophosphate kinase (tmpk) polypeptide in a mammalian cell comprising contacting the mammalian cell with a composition comprising:
- i) a stably integrating lentiviral delivery vector;
- ii) a modified mammalian tmpk polynucleotide wherein the modified mammalian tmpk polynucleotide encodes the modified mammalian tmpk polypeptide that increases phosphorylation of a prodrug relative to phosphorylation of the prodrug by a wild-type mammalian tmpk polypeptide;
- to produce a tmpk modified mammalian cell expressing the modified mammalian tmpk polypeptide;
- b) transplanting the transplant recipient with the isolated tmpk modified mammalian cell;
- wherein the tmpk polypeptide is capable of activating a prodrug to kill the tmpk modified mammalian cell, thereby providing the actuable cell transplant safety component.
A method of treating a subject with a solid tumor comprising:
- a) introducing into the solid tumor a composition comprising:
- i) a stably integrating lentiviral delivery vector;
- ii) a modified mammalian tmpk polynucleotide wherein the modified mammalian tmpk polynucleotide encodes the modified mammalian tmpk polypeptide that increases phosphorylation of a prodrug relative to phosphorylation of the prodrug by a wild-type mammalian tmpk polypeptide;
- to produce a population of tmpk modified mammalian cells expressing the modified mammalian tmpk polypeptide;
- b) administering an amount of a prodrug effective to kill the tmpk modified mammalian cells, to the subject.
Dependencies are inferred from the claim text.