METHOD OF TREATMENT EMPLOYING THERAPEUTIC T CELL PRODUCT FROM MOBILISED DONORS
The present disclosure provides a method of treating a human patient in need thereof with immune reconstitution therapy by administering a therapeutically effective amount of therapeutic T cell population selected and/or expanded from a mobilised blood sample or a mobilised apheresis sample, wherein selection is on the basis of a steady state marker and/or an activation marker optionally followed by expansion, or expansion is in the presence of antigen, such as a viral antigen. It also extends to methods of generating said therapeutic T cell populations and the product obtainable therefrom.
1 . A method of treating a human patient in need thereof with immune reconstitution therapy by administering a therapeutically effective amount of therapeutic T cell population selected and/or expanded from a mobilised blood sample or a mobilised apheresis sample, wherein selection is on the basis of a steady state marker and/or an activation marker optionally followed by expansion, or expansion is in the presence of antigen, such as a viral antigen.
2 . A method according to claim 1 , wherein the patient is post-haematopoietic stem cell transplantation.
3 . A method according to claim 1 , wherein the T cell population is an antigen-specific T cell population.
4 . A method according to claim 3 , wherein the antigen-specific T cell population is specific a virus for example selected from the group comprising cytomegalovirus, adenovirus, varicella zoster virus, BK virus, human papillomavirus, hepatitis B virus, hepatitis C virus, Epstein-Barr virus, Kaposi's sarcoma-associated herpes virus and human T-lymphotropic virus, such as cytomegalovirus or adenovirus.
5 - 28 . (canceled)
29 . A method according to claim 4 , wherein the antigen-specific T cell population is specific to cytomegalovirus.
30 . A method according to claim 29 , wherein the antigen-specific T cell population is specific to pp65.
31 . A method according to claim 1 , wherein the population is directly selected on the basis of a steady state marker namely the T cell receptor, for example by reversible ligation of the T cell receptor by specific HLA:peptide complexes, in particular Tetra, Penta and/or Hexa streptamers.
32 . A method according to claim 1 , wherein the activation marker is a cell surface marker that is upregulated as a consequence of antigen stimulation, for example selected from the group comprising CD25, CD69, CD137 and CD154.
33 . A method according to claim 1 , wherein the T cell population is expanded from a mobilised blood sample or mobilised apheresis sample, in particular expanded in an antigen specific manner.
34 . A method according to claim 1 , wherein the population is substantially negative for cells with the CD25 marker.
35 . A method according to claim 1 , wherein the T cell population is allogeneic.
36 . A method according to claim 1 , wherein the T cell population is selected or expanded from a mobilised apheresis sample.
37 . A method according to claim 1 , wherein the T cell population is selected using Fab-streptamers.
38 . A method according to claim 1 , wherein the T cell population is administered by infusion.