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US 11,440,958 B2Granted
Blockade of CD7 expression and chimeric antigen receptors for immunotherapy of T-cell malignancies
AssigneeNational University of Singapore
InventorsYi Tian Png, Natasha Vinanica, Takahiro Kamiya, Dario Campana
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Abstract
The present invention provides compositions comprising an anti-CD7 chimeric activating receptor (CAR) and an anti-CD7 protein expression blocker, and methods of using such compositions in cancer therapy.
Claims4
An engineered immune cell comprising
- i) a nucleic acid comprising a nucleotide sequence encoding a first single chain variable fragment (scFv) linked to a localizing domain, wherein said first single chain variable fragment (scFv) comprises a heavy chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:1 and a light chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:2, wherein said localizing domain comprises an endoplasmic reticulum (ER) retention sequence comprising an amino acid sequence selected from the group consisting of SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:13, and wherein said first scFv linked to said localizing domain downregulates or suppresses surface expression of endogenous CD7 in the engineered cell rendering CD7 inactive;
- and
- ii) a nucleic acid comprising a nucleotide sequence encoding an anti-CD7 chimeric antigen receptor (CAR), wherein said CAR comprises a 4-1BB intracellular signaling domain, a CD3ζ intracellular signaling domain, and a second single chain variable fragment (scFv) comprises a heavy chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:1 and a light chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:2, wherein the second scFv is expressed on the surface of the engineered immune cell.
An engineered immune cell comprising
- i) a nucleic acid comprising a nucleotide sequence encoding a first single chain variable fragment (scFv) linked to a localizing domain, wherein said a first single chain variable fragment (scFv) comprises a heavy chain variable domain having the amino acid sequence of SEQ ID NO:1 and a light chain variable domain having the amino acid sequence of SEQ ID NO:2, wherein said localizing domain comprises an endoplasmic reticulum (ER) retention sequence comprising an amino acid sequence selected from the group consisting of SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:13, wherein said first scFv linked to said localizing domain downregulates or suppresses surface expression of endogenous CD7 in the engineered cell rendering CD7 inactive;
- and
- ii) a nucleic acid comprising a nucleotide sequence encoding an anti-CD7 chimeric antigen receptor (CAR), wherein said CAR comprises a 4-1BB intracellular signaling domain, a CD3ζ intracellular signaling domain, and a second single chain variable fragment (scFv) comprises a heavy chain variable domain having the amino acid sequence of SEQ ID NO:1 and a light chain variable domain having the amino acid sequence of SEQ ID NO:2, wherein the second scFv is expressed on the surface of the engineered immune cell.
An engineered immune cell comprising
- i) a nucleic acid comprising a nucleotide sequence encoding a first single chain variable fragment (scFv) linked to a localizing domain, wherein said first single chain variable fragment (scFv) comprises a heavy chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:
- 1 and a light chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:2, wherein said localizing domain comprises an endoplasmic reticulum (ER) retention sequence comprising an amino acid sequence selected from the group consisting of SEQ ID NO:8, SEQ ID NO:9, and SEQ ID NO:13, and wherein said first scFv linked to said localizing domain downregulates or suppresses surface expression of endogenous CD7 in the engineered cell rendering CD7 inactive;
- and
- ii) a nucleic acid comprising a nucleotide sequence encoding an anti-CD7 chimeric antigen receptor (CAR), wherein said CAR comprises a 4-1BB intracellular signaling domain, a CD3ζ intracellular signaling domain, and a second single chain variable fragment (scFv) comprises a heavy chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:14 and a light chain variable domain having at least 90% sequence identity to the amino acid sequence of SEQ ID NO:15, wherein the second scFv expressed on the surface of the engineered immune cell.
1 more element
An engineered immune cell comprising:
- i) a nucleic acid comprising a nucleotide sequence encoding a first single chain variable fragment (scFv) linked to a localizing domain, wherein said a first single chain variable fragment (scFv) comprises a heavy chain variable domain having the amino acid sequence of SEQ ID NO:1 and a light chain variable domain having the amino acid sequence of SEQ ID NO:2, wherein said localizing domain comprises an endoplasmic reticulum (ER) retention sequence comprising an amino acid sequence of SEQ ID NO:8, wherein said first scFv linked to said localizing domain downregulates or suppresses surface expression of endogenous CD7 in the engineered cell rendering CD7 inactive;
- and
- ii) a nucleic acid comprising a nucleotide sequence encoding an anti-CD7 chimeric antigen receptor (CAR), wherein said CAR comprises a 4-1BB intracellular signaling domain, a CD3ζ intracellular signaling domain, and a second single chain variable fragment (scFv) comprises a heavy chain variable domain having the amino acid sequence of SEQ ID NO:1 and a light chain variable domain having the amino acid sequence of SEQ ID NO:2, wherein the second scFv is expressed on the surface of the immune cell surface.
Dependencies are inferred from the claim text.