US2017160267A9PendingUtilityA9
Methods of determining cellular chemosensitivity
Assignee: DANA FARBER CANCER INST INCPriority: Mar 31, 2006Filed: Mar 17, 2016Published: Jun 8, 2017
Est. expiryMar 31, 2026(expired)· nominal 20-yr term from priority
Inventors:Anthony Letai
G01N 2800/52G01N 2510/00G01N 33/521C12Q 1/025C12N 15/1037G01N 33/5011A61P 35/00G01N 33/57575G01N 33/575
60
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Claims
Abstract
The present invention provides methods of determining cell sensitivity to a therapeutic agent.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A composition comprising an isolated permeabilized cell containing:
a BH3 domain peptide of less than or equal to 50 amino acids in length, and a mitochondrion.
2 . The composition of claim 1 , wherein the BH3 domain peptide is selected from a BID BH3 domain, a BIM BH3 domain, a BAD BH3 domain, a BIK BH3 domain, a NOXA BH3 domain, a PUMA BH3 domain, a BMF BH3 domain, and an HRK BH3 domain.
3 . The composition of claim 1 , wherein the BH3 domain peptide contains an amino acid sequence selected from SEQ ID NOs: 1-11.
4 . The composition of claim 1 , wherein the cell is permeabilized by being contacted with digitonin.
5 . The composition of claim 1 , wherein the BH3 domain peptide is less than or equal to 35 amino acids in length, less than or equal to 25 amino acids in length, or less than or equal to 15 amino acids in length.
6 . The composition of claim 1 , wherein the isolated BH3 domain peptide is complexed with BCL-2, BCL-XL, MCL-1, BFL-1 or BCL-w protein in the cell.
7 . The composition of claim 1 , wherein the permeabilized cell is a cancer cell.
8 . The composition of claim 7 , wherein the cancer cell overexpresses BCL-2, BCL-XL, MCL-1, BFL-1 or BCL-w protein.
9 . The composition of claim 7 , wherein the cancer cell is a lymphoma cell, a leukemia cell, or a small cell lung cancer cell.
10 . The composition of claim 1 , wherein the isolated cell further contains a potentiometric dye.
11 . The composition of claim 10 , wherein the potentiometric dye is JC-1.
12 . A composition comprising an isolated permeabilized cell contacted with an isolated BH3 domain peptide of less than or equal to 50 amino acids in length, wherein the isolated permeabilized cell contains a mitochondrion.
13 . The composition of claim 12 , wherein the BH3 domain peptide is selected from a BID BH3 domain, a BIM BH3 domain, a BAD BH3 domain, a BIK BH3 domain, a NOXA BH3 domain, a PUMA BH3 domain, a BMF BH3 domain, and an HRK BH3 domain.
14 . The composition of claim 12 , wherein the BH3 domain peptide contains an amino acid sequence selected from SEQ ID NOs: 1-11.
15 . The composition of claim 12 , wherein the cell is permeabilized by being contacted with digitonin.
16 . The composition of claim 12 , wherein the isolated BH3 domain peptide is complexed with BCL-2, BCL-XL, MCL-1, BFL-1 or BCL-w protein in the cell.
17 . The composition of claim 12 , wherein the permeabilized cell is a cancer cell.
18 . The composition of claim 17 , wherein the cancer cell overexpresses BCL-2, BCL-XL, MCL-1, BFL-1 or BCL-w protein.
19 . The composition of claim 17 , wherein the cancer cell is a lymphoma cell, a leukemia cell, or a small cell lung cancer cell.
20 . The composition of claim 12 , wherein the isolated cell is further contacted with a potentiometric dye.
21 . The composition of claim 20 , wherein the potentiometric dye is JC-1.
22 . A composition comprising an isolated permeabilized cell containing:
a complex of BCL-2, BCL-XL, MCL-1, BFL-1 or BCL-w protein and a BH3 domain peptide of less than or equal to 50 amino acids in length, and a mitochondrion.
23 . The composition of claim 22 , wherein the BH3 domain peptide is selected from a BID BH3 domain, a BIM BH3 domain, a BAD BH3 domain, a BIK BH3 domain, a NOXA BH3 domain, a PUMA BH3 domain, a BMF BH3 domain, and an HRK BH3 domain.
24 . The composition of claim 22 , wherein the BH3 domain peptide contains an amino acid sequence selected from SEQ ID NOs: 1-11.
25 . The composition of claim 22 , wherein the cell is permeabilized by being contacted with digitonin.
26 . The composition of claim 22 , wherein the permeabilized cell is a cancer cell.
27 . The composition of claim 26 , wherein the cancer cell overexpresses BCL-2, BCL-XL, MCL-1, BFL-1 or BCL-w protein.
28 . The composition of claim 26 , wherein the cancer cell is a lymphoma cell, a leukemia cell, or a small cell lung cancer cell.
29 . The composition of claim 22 , wherein the isolated cell further contains a potentiometric dye.
30 . The composition of claim 29 , wherein the potentiometric dye is JC-1.Join the waitlist — get patent alerts
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