Enhanced adoptive cell therapy
AssigneeWerewolf Therapeutics, Inc.
InventorsWilliam WINSTON, Cynthia SEIDEL-DUGAN, Jose Andres SALMERON-GARCIA, Randi ISAACS, Connor Jude DWYER, Kristin R. MORRIS
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Abstract
The disclosure relates to combination therapy comprising an inducible cytokine prodrug and an adoptive cell therapy. The disclosure also relates to methods for treating subjects using such combinations.
Claims109
A method of treating a subject in need thereof, comprising administering to the subject an effective amount of:
- a) an inducible cytokine prodrug, and
- b) an adoptive cell therapy.
A method of treating a subject in need thereof, comprising administering to the subject an effective amount of:
- a) an inducible cytokine prodrug, and
- b) a polynucleotide encoding an antigen binding protein.
A method of treating a subject in need thereof, comprising administering to the subject an effective amount of:
- a) a polynucleotide encoding an inducible cytokine prodrug, and
- b) an adoptive cell therapy.
A method of treating a subject in need thereof, comprising administering to the subject an effective amount of:
- a) a polynucleotide encoding an inducible cytokine prodrug, and
- b) a polynucleotide encoding an antigen binding protein.
A method of treating a subject in need thereof, comprising administering to the subject an effective amount of:
- a) A polynucleotide encoding an inducible cytokine prodrug and an antigen binding protein.
A method of treating a subject in need thereof, comprising administering to the subject an effective amount of:
- a) An immune cell comprising a polynucleotide encoding an inducible cytokine prodrug.
The method of any preceding claim, wherein the inducible cytokine prodrug comprises:
- a) a cytokine polypeptide,
- b) a protease cleavable linker, and
- c) a blocking element,
- wherein the inducible cytokine prodrug has attenuated biological activity and wherein cleavage of the protease cleavable linker by a protease produces a cytokine polypeptide with biological activity that is not attenuated.
The method of any preceding claim, wherein the second subunit protein is endogenous to the subject.
The method of 59, wherein the TFP comprises a sequence selected from SEQ ID NO:
- 703-705.
The method of any of claims 17-70, wherein the inducible cytokine prodrug has a half-life of at least about 1 hour, or wherein the inducible cytokine prodrug has a half-life of at least about 2 hours, or wherein the inducible cytokine prodrug has a half-life of at least about 3 hours, or wherein the inducible cytokine prodrug has a half-life of at least about 4 hours, or wherein the inducible cytokine prodrug has a half-life of at least about 5 hours, or wherein the inducible cytokine prodrug has a half-life of at least about 6 hours, or wherein the inducible cytokine prodrug has a half-life of at least about 7 hours, or wherein the inducible cytokine prodrug has a half-life of at least about 8 hours, or wherein the inducible cytokine prodrug has a half-life of at least about 9 hours, or wherein the inducible cytokine prodrug has a half-life of at least about 10 hours, or wherein the inducible cytokine prodrug has a half-life of at least about 11 hours, or wherein the inducible cytokine prodrug has a half-life of at least about 12 hours, or wherein the inducible cytokine prodrug has a half-life of at least about 18 hours, or wherein the inducible cytokine prodrug has a half-life of at least about 24 hours.
The method of any preceding claim, further comprising the step of administering a chemotherapeutic agent.
The method of any preceding claim, further comprising the step of administering a checkpoint inhibitor.
The method of any preceding claim, wherein 2 or more inducible cytokine prodrugs comprising different cytokines, muteins, subunits, or functional fragments thereof are administered.
A pharmaceutical composition comprising:
- a) A inducible cytokine prodrug comprising:
- i) A cytokine polypeptide selected from the group IL-2, IL-12, IL-15, and IL-21, or a functional fragment, mutein or subunit thereof,
- ii) A cleavable linker comprising an amino acid sequence selected from SEQ ID NOs:
- 195-220 or an amino acid sequence that has at least about 90% identity to SEQ ID NOs:
- 195-220, and
- iii) A blocking element selected from a steric blocking element, a specific blocking element, and the combination thereof, and
- b) An adoptive cell therapy.
A polynucleotide encoding:
- a) A inducible cytokine prodrug comprising:
- i) A cytokine polypeptide selected from the group IL-2, IL-12, IL-15, and IL-21, or a functional fragment, mutein or subunit thereof,
- ii) A cleavable linker comprising an amino acid sequence selected from SEQ ID NOs:
- 195-220 or an amino acid sequence that has at least about 90% identity to SEQ ID NOs:
- 195-220, and
- iii) A blocking element selected from a steric blocking element, a specific blocking element, and the combination thereof, and
- b) An antigen binding protein.
An immune cell comprising:
- a) A polynucleotide encoding an inducible cytokine prodrug comprising:
- i) A cytokine polypeptide selected from the group IL-2, IL-12, IL-15, and IL-21, or a functional fragment, mutein or subunit thereof,
- ii) A protease cleavable linker comprising an amino acid sequence selected from SEQ ID NOs:
- 195-220 or an amino acid sequence that has at least about 90% identity to SEQ ID NOs:
- 195-220, and
- iii) A blocking element selected from a steric blocking element, a specific blocking element, and the combination thereof, and
- b) A polynucleotide encoding an antigen binding protein.
A method of making an immune cell comprising contacting an immune cell with a (one or more) polynucleotide encoding:
- a) A inducible cytokine prodrug comprising:
- i) A cytokine polypeptide selected from the group IL-2, IL-12, IL-15, and IL-21, or a functional fragment, mutein or subunit thereof,
- ii) A protease cleavable linker comprising an amino acid sequence selected from SEQ ID NOs:
- 195-220 or an amino acid sequence that has at least about 90% identity to SEQ ID NOs:
- 195-220, and
- iii) A blocking element selected from a steric blocking element, a specific blocking element, and the combination thereof.
Dependencies are inferred from the claim text.