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1. WO2020160285 - EXPRESSION DE SIRPα SUR LYMPHOCYTES T COMME BIOMARQUEUR DE LYMPHOCYTES T FONCTIONNELS DURANT L’ÉPUISEMENT

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[ EN ]

WHAT IS CLAIMED IS:

1. A method of determining whether a cell or cell population is responsive to a therapeutic regimen to activate and expand exhausted CD8+ T cells, the method comprising:

assaying a cell sample from an individual to determine if functional CD8+, SIRPα+ functional T cells are present.

2. The method of claim 1, comprising contacting a population of T cells with an affinity agent for SIRPα, and detecting the presence of bound agent.

3. The method of claim 2, further comprising detecting the presence of PD-1 and/or CD8 on the T cells.

4. The method of any of claims 1-3 wherein the biological sample is one or more of a swab, skin sample, blood sample, a biopsy sample, a fine needle aspirate.

5. The method of any of claims 1-4, wherein the cell sample is obtained from an individual with cancer.

6. The method of any of claims 1-4, wherein the cell sample is obtained from an individual with a chronic infection.

7. The method of any of claims 1-6, wherein functional T cells positive for SIRPa and one or more inhibitory receptors selected from PD-1, CTLA-4, LAG-3, TIM-3.

8. The method of any of claims 1-7, wherein the functional CD8+ T cells are specific for a tumor antigen or a pathogen antigen.

9. The method of any of claims 1-8, wherein the patient is treated with a regimen to expand CD8+, SIRPα+ functional T cells.

10. The method of claim 9, wherein the regimen comprises blockade of inhibitory receptors.

11. The method of ciaim 10 wherein the patient is treated with a regimen comprising blockade of PD-1/PD-L1.

12. The method of claim 11 wherein the regimen comprises administering an effective dose of an antibody that blocks PD-1/PD-L1.

13. The method of any of claims 9-12, further comprising obtaining a patient sample following the regimen, to determine if there is an expansion of CD8+, SIRPα+ functional T cells.

14. A method of isolating functional PD-1+CD8+ T cells, the method comprising isolating from a population of such T cells, cells that co-express SIRPα.

15. The method of claim 14, wherein the T cells thus isolated are analyzed for antigenic specificity to identify appropriate antigens for stimulation.

16. The method of claim 14, wherein the T cells thus isolated are stimulated and expanded in culture.

17. The method of claim 16, wherein the expanded T cell population is reintroduced into the individual for therapeutic purposes.

18. The method of claim 15, wherein the cognate antigen is provided in combination with a regimen in order to stimulate the CD8+, SIRPα+ functional T cells.