Granted Patent
B2
US 12,539,308 · App. 16/960,508 · Granted Feb 3, 2026
Immune-enhancing RNAs for combination with chimeric antigen receptor therapy
Inventors:
Lexus R. Johnson (Philadelphia, PA); Carl H. June (Merion Station, PA); Andy J. Minn (Philadelphia, PA)
A61K31/7088A61K39/39558A61K40/11A61K40/31A61K40/4211A61P35/00C12N15/117A61K31/4439A61K39/39A61K2039/505A61K2039/55561A61K2039/876A61K2239/38A61K2239/57
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Abstract
The invention provides compositions and methods for treating diseases such as cancer. The invention also relates to a method of administering a chimeric antigen receptor (CAR) therapy and an additional therapeutic agent.
Claims (26)
1 . An exogenous nucleic acid molecule comprising:
(a) a first nucleic acid sequence encoding a chimeric antigen receptor (CAR) that binds to an antigen, and
(b) a second nucleic acid sequence encoding an RNA molecule, wherein the RNA molecule activates a pattern recognition receptor (PRR), and further wherein the RNA molecule is a RN7SL1 RNA molecule, or the RNA molecule comprises a nucleotide sequence having at least 95% identity to SEQ ID NO: 2, 4, 6, 8, or 10 wherein the RNA molecule retains all or part of the immunogenic property of the naturally-existing RN7SL1 RNA molecule.
2 . An isolated immune cell comprising the exogenous nucleic acid molecule of claim 1 .
3 . A population of cells comprising the isolated immune cell of claim 2 .
4 . A pharmaceutical composition comprising the population of isolated cells of claim 3 and a pharmaceutically acceptable carrier, excipient, or stabilizer.
5 . A method for treating cancer, the method comprising administering to the subject an effective amount of the pharmaceutical composition of claim 4 .
6 . A method of making the cell of claim 2 , comprising: (1) providing an isolated immune cell, comprising a first exogenous nucleic acid molecule comprising a nucleic acid sequence encoding the chimeric antigen receptor (CAR) comprising a first antigen binding domain that binds to a first antigen, and (2) contacting the cell ex vivo with the second exogenous nucleic acid molecule comprising at least one nucleic acid sequence comprising or encoding the exogenous RNA molecule.
7 . A kit comprising the exogenous nucleic acid molecule of claim 1 .
8 . A method of making a CAR-expressing cell, comprising introducing the nucleic acid molecule of claim 1 into an immune effector cell under a condition such that the CAR molecule is expressed.
9 . The exogenous nucleic acid molecule of claim 1 , wherein the CAR comprises, in an N- to C-terminal orientation, an antigen binding domain that binds to the antigen, a transmembrane domain, and an intracellular signaling domain, wherein the antigen binding domain is connected to the transmembrane domain by a hinge domain.
10 . The exogenous nucleic acid molecule of claim 1 , wherein the antigen is a tumor antigen.
11 . The immune cell of claim 2 , wherein when the PRR is expressed in an isolated immune cell, the isolated immune cell is a dendritic cell (DC), a macrophage, or a T cell.
12 . The exogenous nucleic acid molecule of claim 1 , wherein the RNA molecule comprises RN7SL1.
13 . The exogenous nucleic acid molecule of claim 1 , wherein the second nucleic acid sequence encoding the RNA molecule comprises the sequence of SEQ ID NO: 1.
14 . The exogenous nucleic acid molecule of claim 1 , wherein the RNA molecule comprises an Alu-Ya5, wherein the Alu-Ya5 comprises the nucleotide sequence of SEQ ID NO: 8.
15 . The exogenous nucleic acid molecule of claim 1 , wherein the second nucleic acid sequence encoding the RNA molecule comprises the sequence of SEQ ID NO: 7.
16 . The exogenous nucleic acid molecule of claim 1 , wherein the RNA molecule comprises a hairpin RN7SL1, wherein the hairpin RN7SL1 comprises the nucleotide sequence of SEQ ID NO: 10.
17 . The exogenous nucleic acid molecule of claim 1 , wherein the second nucleic acid sequence encoding the RNA molecule comprises the sequence of SEQ ID NO: 9.
18 . The isolated immune cell of claim 2 , wherein the CAR comprises, in an N- to C-terminal orientation, an antigen binding domain that binds to the antigen, a transmembrane domain, and an intracellular signaling domain, wherein the antigen binding domain is connected to the transmembrane domain by a hinge domain.
19 . The isolated immune cell of claim 2 , wherein the isolated immune cell comprises a T cell or an NK cell.
20 . The isolated immune cell of claim 2 , wherein the antigen is a tumor antigen.
21 . The isolated immune cell of claim 2 , wherein the RNA molecule comprises RN7SL1 or a fragment thereof.
22 . The isolated immune cell of claim 1 , wherein the RNA molecule comprises the sequence of SEQ ID NO: 2, 4, or 6.
23 . The isolated immune cell of claim 2 , wherein the RNA molecule comprises an Alu-Ya5, wherein the Alu-Ya5 comprises the nucleotide sequence of SEQ ID NO: 8.
24 . The isolated immune cell of claim 2 , wherein the RNA molecule comprises a hairpin RN7SL1, wherein the hairpin RN7SL1 comprises the nucleotide sequence of SEQ ID NO: 10.
Continuity (3)
Provisional Application
62614908
· Jan 8, 2018
Provisional Application
62653932
· Apr 6, 2018
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