Tscm CELLS AND METHODS FOR USE
The present invention relates to TSCM cells and uses thereof. TSCM cells can be used help identify and treat patients who are likely to experience particular treatment outcomes. In other embodiments TSCM cells are generated in vitro and used for adoptive transfer therapy.
1 . A method for obtaining an autologous population of cells enriched for T SCM cells suitable for introduction into a human patient comprising the steps of:
a) preparing PME-CD40L mature DCs from a human patient;
b) culturing PBMCs obtained from said patient in vitro with said PME-CD40L mature DCs in a coculture for a time sufficient to induce an increase in the number of T SCM cells in said coculture;
c) enriching said T SCM cells from said coculture.
2 . The method of claim 1 , wherein said PME-CD40L mature DCs are loaded with an antigen.
3 . The method of claim 2 , wherein said DCs are loaded with said antigen by transfection with RNA encoding said antigen.
4 . The method of claim 3 , wherein said RNA is prepared from cells of an HIV-infected patient.
5 . The method of claim 3 , wherein said antigen is prepared from cancer cells of a cancer patient.
6 . The method of claim 5 , wherein said T SCM cells are CD8+, CD95+, CD28+, CCR7+, and CD45RA+.
7 . The method of claim 1 , wherein said T SCM cells are CD27 + , CD28 + , and CD45RA + .
8 . The method of claim 7 , wherein said T SCM cells are enriched as cells positive for CD27, CD28, and CD45RA.
9 . The method of claim 1 , further comprising combining said T SCM cells with a pharmaceutically acceptable carrier.
10 . A method for producing a population of T SCM cells from a patient that are reactive to an antigen of interest comprising the steps of:
a) preparing PME-CD40L mature DCs from a human patient;
b) culturing T SCM cells obtained from said patient in vitro with said PME-CD40L mature DCs in a coculture for a time sufficient to induce an increase in the number of T SCM cells in said coculture;
c) enriching said T SCM cells from said coculture.
11 . The method of claim 10 , wherein said T SCM cells are CD8+, CD95+, CD28+, CCR7+, and CD45RA+.
12 . The method of claim 10 , wherein said T SCM cells are enriched as cells positive for CD27, CD28, and CD45RA.
13 . A method of inducing an immune response in a patient comprising administering to said patient cells produced by the method of claim 1 .
14 . A method of determining whether an immune response was induced in a patient by a treatment, comprising the steps of:
a) quantifying the number of T SCM cells present in a sample of a patient's blood to establish a baseline reading;
b) following administration to said patient of a treatment, quantifying the number of T SCM cells present in a sample of said patient's blood to establish a post-treatment reading;
c) comparing said baseline reading and said post-treatment reading to determine whether the frequency or amount of T SCM cells present in the sample of the patient's blood has increased;
wherein a significant increase in the frequency or amount of T SCM cells indicates that an immune response was induced in the patient.
15 . The method of claim 14 , wherein said treatment comprises administering to said patient autologous mature DCs prepared in vitro.