Cell Co-Culture Systems and Uses Thereof
AssigneeDana-Farber Cancer Institute, Inc.
InventorsConstantine S. Mitsiades, Douglas W. McMillin, Joseph M. Negri, Nicholas Mitsiades, Kenneth C. Anderson
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Abstract
The invention provides a cell co-culture for the selective evaluation of the response of a cell of interest in the co-culture, and methods of using the co-culture. The cell co-culture and the methods are suitable for large-scale/high throughput screening for compounds useful for affecting at least one biological function or event of at least one cell type in the co-culture. The invention further provides kits for using the screening assays.
Claims24
1-43. (canceled)
A method for identifying a compound useful for modulating a cellular biological activity of interest in cells of the first cellular compartment, the method comprising:
- (1) contacting the cell co-culture system of claim 1 with a test compound;
- (2) detecting the signal generated by the compartment-specific marker from the cell co-culture system in the presence and absence of the test compound;
- wherein a statistically significant difference in the signal after contact with the test compound compared to the signal in the absence of the test compound is indicative that the test compound is capable of modulating the cellular biological activity of interest in cells of the first cellular compartment in the presence of cells in the second compartment.
A method for identifying a compound useful for modulating a cellular biological activity of interest in the first cellular compartment, the method comprising:
- (1) contacting the cell co-culture system of claim 1 with a test compound;
- (2) contacting, under substantially the same conditions, a second cell culture comprising the first cellular compartment but not the second cellular compartment with the test compound;
- (3) detecting the signal generated by the compartment-specific marker from the cell co-culture system and the second cell culture;
- wherein a statistically significant decrease in the signal from the cell co-culture system compared to that of the second cell culture is indicative that the test compound is capable of modulating, the cellular biological activity of interest in cells of the first cellular compartment.
A method for identifying a treatment useful for modulating a cellular biological activity of interest, the method comprising:
- (1) subjecting the cell co-culture system of claim 1 to said treatment;
- (2) detecting the signal generated by the compartment-specific marker from the cell co-culture system in the presence and in the absence of the treatment;
- wherein a statistically significant change in the signal after the treatment compared to that without the treatment is indicative that the treatment is useful for modulating the cellular biological activity of interest in cells of the first cellular compartment.
57-66. (canceled)
A method of identifying a compound that overcomes accessory cell-mediated tumor cell resistance to an anti-tumor compound, the method comprising:
- (1) contacting the cell co-culture system of claim 1 with a test compound and the anti-tumor compound,
- wherein said first cellular compartment comprises a tumor cell, and said second cellular compartment comprises non-tumor accessory cells, and,
- wherein the accessory cells confer accessory cell-mediated tumor cell resistance to the anti-tumor compound;
- (2) detecting the signal generated by the compartment-specific marker from the cell co-culture system in the presence and absence of the test compound;
- wherein a statistically significant change in the signal after contacting with the test compound compared to that before contacting the candidate compound is indicative that the candidate compound overcomes accessory cell-mediated tumor cell resistance to the anti-tumor drug.
69-71. (canceled)
A method for identifying a compound useful for treating cancer, the method comprising:
- (1) contacting the mammalian cell co-culture system of claim 69 with one or more candidate compounds;
- (2) detecting the signal generated by the compartment-specific bioluminescent marker from the cell co-culture system in the presence and absence of the candidate compounds;
- wherein a statistically significant decrease in the signal after contacting with the candidate compound compared to that before contacting with the candidate compound is indicative that the candidate compound is useful for treating cancer.
A method for identifying a compound useful for treating cancer, the method comprising:
- (1) providing a cell co-culture system of claim 69, and in parallel, a second cell culture comprising the tumor cell compartment but not the accessory cell compartment;
- (2) contacting, under substantially the same conditions, the cell co-culture system and the second cell culture with a candidate compound;
- (3) detecting the signal generated by the compartment-specific bioluminescent marker from the cell co-culture system and the second cell culture;
- wherein a statistically significant decrease in the signal from the cell co-culture system compared to that of the second cell culture is indicative that the candidate compound is useful for treating cancer.
Dependencies are inferred from the claim text.