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US 2021/0171601 A1Published application
Leucine zipper-based compositions and methods of use
AssigneeMemorial Sloan Kettering Cancer Center
InventorsScott E. JAMES, Marcel R.M. VAN DEN BRINK, Lorenz JAHN
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Abstract
The presently disclosed subject matter provides compositions and systems for cell-based immunotherapy. In certain non-limiting embodiments, the system comprises a membrane-bound polypeptide and at least one soluble polypeptide that is capable of dimerizing with the membrane-bound polypeptide.
Claims52
A system, comprising:
- a) a membrane-bound polypeptide comprising:
- i) a transmembrane domain, ii) an intracellular domain, and iii) an extracellular domain that comprises a first dimerization domain and a blocking spacer, and
- b) a soluble polypeptide comprising i) a second dimerization domain, and ii) an antigen binding domain that binds to an antigen,
- wherein each of the first dimerization domain and the second dimerization domain comprises a leucine zipper domain, and the blocking spacer prevents dimerization of the membrane-bound polypeptide with the soluble polypeptide when the membrane-bound polypeptide and the soluble polypeptide are not expressed from the same cell.
1 more element
A system, comprising:
- a) a membrane-bound polypeptide comprising:
- i) a transmembrane domain, ii) an intracellular domain, and iii) an extracellular domain that comprises a first dimerization domain and a second dimerization domain that is capable of dimerizing with the first dimerization domain, and
- b) a soluble polypeptide comprising i) a third dimerization domain that is capable of dimerizing with the first dimerization domain, and ii) an antigen binding domain that binds to an antigen,
- wherein each of the first dimerization domain and the second dimerization domain comprises a leucine zipper domain.
1 more element
A system, comprising:
- a) a membrane-bound polypeptide comprising a transmembrane domain, an intracellular domain and an extracellular domain that comprises a first dimerization domain, and
- b) a soluble polypeptide comprising a second dimerization domain that is capable of dimerizing with the first dimerization domain, and a cytokine or a chemokine,
- wherein each of the first dimerization domain and the second dimerization domain comprises a leucine zipper domain.
A nucleic acid composition comprising
- (a) a first polynucleotide encoding a membrane-bound polypeptide comprising:
- i) a transmembrane domain, ii) an intracellular domain, and iii) an extracellular domain that comprises a first dimerization domain and a blocking spacer, and
- (b) a second polynucleotide encoding a soluble polypeptide comprising i) a second dimerization domain, and ii) an antigen binding domain that binds to an antigen,
- wherein each of the first dimerization domain and the second dimerization domain comprises a leucine zipper domain, and the blocking spacer prevents dimerization of the membrane-bound polypeptide with the soluble polypeptide when the membrane-bound polypeptide and the soluble polypeptide are not expressed from the same cell.
1 more element
A nucleic acid composition comprising
- (a) a first polynucleotide encoding a membrane-bound polypeptide comprising:
- i) a transmembrane domain, ii) an intracellular domain, and iii) an extracellular domain that comprises a first dimerization domain and a second dimerization domain that is capable of dimerizing with the first dimerization domain, and
- (b) a second polynucleotide encoding a soluble polypeptide comprising i) a third dimerization domain that is capable of dimerizing with the first dimerization domain, and ii) an antigen binding domain that binds to an antigen,
- wherein each of the first dimerization domain and the second dimerization domain comprises a leucine zipper domain.
1 more element
A nucleic acid composition comprising
- (a) a first polynucleotide encoding a membrane-bound polypeptide comprising a transmembrane domain and an extracellular domain that comprises a first dimerization domain, and
- (b) a second polynucleotide encoding a soluble polypeptide comprising a second dimerization domain that is capable of dimerizing with the first dimerization domain, and a cytokine or a chemokine,
- wherein each of the first dimerization domain and the second dimerization domain comprises a leucine zipper domain.
Dependencies are inferred from the claim text.