Biomarkers for determining the clinical response to cell therapy
The invention relates to a method for predicting the clinical response to a therapy based on the administration of mesenchymal stem cells (MSCs) in a patient suffering from an immune-mediated inflammatory disease. The invention also relates to methods of personalised medicine as well as to therapeutic uses of MSCs in a patient suffering from an immune-mediated inflammatory disease.
1. A method for selecting and treating a patient suffering from an immune-mediated inflammatory disease, the method comprising:
(a) obtaining a blood sample from a patient;
(b) determining in said sample from the patient at least one parameter selected from the group consisting of:
(i) the level of monocytes,
(ii) the level of T reg cells,
(iii) the ratio of CD4+ T cells to T reg cells (CD4+/T reg ), and
(iv) the T cell proliferation capacity,
(c) comparing the parameters in said sample with their reference values;
(d) selecting a patient as likely to show a clinical response to a therapy comprising the administration of mesenchymal stem cells (MSCs) wherein the patient has at least one parameter selected from the group consisting of:
an increased level of monocytes in said sample with respect to a reference value, wherein the reference value is obtained from the value of the level of monocytes in a blood sample from one or more patients who do not respond to a therapy based on comprising the administration of MSCs,
a decreased level of T reg cells with respect to a reference value, wherein the reference value is obtained from the value of the level of T reg cells in a blood sample from one or more patients who do not respond to a therapy comprising the administration of MSCs,
an increased ratio of CD4+ T cells to T reg cells (CD4+/T reg ) with respect to a reference value, wherein the reference value is obtained from the value of the ratio of CD4+ T cells to T reg cells (CD4+/T reg ) in a blood sample from one or more patients who do not respond to a therapy comprising the administration of MSCs, and
an increased T cell proliferation capacity with respect to a reference value,
wherein the reference value is obtained from the value of the T cell proliferation capacity in a blood sample from one or more patients who do not respond to a therapy comprising the administration of MSCs; and
(e) administering a therapy comprising the administration of MSCs to the patient selected in step (d) as likely to show a clinical response to the therapy.
2. The method according to claim 1 , wherein said immune-mediated inflammatory disease is rheumatoid arthritis.
3. The method according to claim 2 , wherein said rheumatoid arthritis is refractory.
4. The method according to claim 1 , wherein the MSCs are allogeneic stem cells.
5. The method according to claim 4 , wherein the stem cells are adipose tissue derived stromal stem cells (ASCs).
6. The method according to claim 5 , wherein the ASCs are expanded ASCs.
7. The method according to claim 1 , wherein administration of MSCs is intravenous.
8. A method for the treatment of an immune-mediated inflammatory disease in a patient in need thereof, the method comprising the steps of:
(a) selecting a patient having at least one parameter selected from the group consisting of:
an increased level of monocytes with respect to a reference value, wherein the reference value is obtained from the value of the level of monocytes in a blood sample from one or more patients who do not respond to a therapy comprising the administration of MSCs,
a decreased level of T reg cells with respect to a reference value, wherein the reference value is obtained from the value of the level of Treg cells in a blood sample from one or more patients who do not respond to a therapy comprising the administration of MSCs,
an increased CD4+/T reg ratio with respect to a reference value, wherein the reference value is obtained from the value of the ratio of CD4+ T cells to T reg cells (CD4+/T reg ) in a blood sample from one or more patients who do not respond to a therapy comprising the administration of MSCs, and
an increased T cell proliferation capacity with respect to a reference value, wherein the reference value is obtained from the value of the T cell proliferation capacity in a blood sample from one or more patients who do not respond to a therapy comprising the administration of MSCs; and
(b) administering MSCs to the patient selected in step (a).
9. The method according to claim 8 , wherein the MSCs are allogeneic stem cells.
10. The method according to claim 8 , wherein the stem cells are adipose tissue derived stromal stem cells (ASCs).
11. The method according to claim 10 , wherein the ASCs are expanded ASCs.
12. The method according to claim 8 , wherein the MSCs are administered systemically or locally.
13. The method according to claim 8 , wherein said immune-mediated inflammatory disease is rheumatoid arthritis.
14. The method according to claim 13 , wherein said rheumatoid arthritis is refractory.
15. The method according to claim 14 , wherein the patient is refractory to at least one biological treatment.
16. The method according to claim 15 , wherein said at least one biological treatment is a TNF-α inhibitor, IL-1 inhibitor, IL-6 inhibitor, or T cell-costimulation inhibitor, or an anti-CD20 antibody.
17. The method according to claim 16 , wherein:
the TNF-α inhibitor is Adalimumab, Certolizumab, Etanercept, Golimumab, Rituximab, or Infliximab; the IL-1 inhibitor is anakinra; the IL-6 inhibitor is tocilizumab; the T cell-costimulation inhibitor is Abatacept; and the anti-CD20 antibody is rituximab.