Patent ID: 11896615
Assignee: JUNO THERAPEUTICS, INC.
Field: Pharmaceuticals (Chemistry)
Classification: CPC A  C  G | IPC A  C  G

Claim 13:
14. The method of claim 1, wherein the method results in:
an increase in tryptophan levels or a decrease in kynurenine levels in the tumor or in a biological sample from the subject, compared to a method involving administration of the T cell therapy but in the absence of the inhibitor of IDO1;
increased or prolonged expansion or persistence of T cells of the T cell therapy in the subject as compared to a method in which the T cell therapy is administered to the subject in the absence of the inhibitor of IDOL or a method in which a similar T cell is administered but in which the T cells do not comprise modification of expression of a molecule associated with DO-mediated immunosuppressive signaling, associated with sensing or responding to tryptophan starvation or insufficiency or associated with sensing or responding to kynurenine-mediated immuno-suppression;
reduced expression or level of CD25 on the surface of the cells of the T cell therapy following said administration to the subject as compared to the expression or level in a method in which the T cell therapy is administered to the subject in the absence of the inhibitor of IDOL or a method in which a similar T cell therapy is administered but in which the T cells do not comprise modification of expression of a molecule associated with IDO-mediated immunosuppressive signaling, associated with sensing or responding to tryptophan starvation or insufficiency or associated with sensing or responding to kynurenine-mediated immuno-suppression;
an increase in tryptophan levels, a decrease in kynurenine levels or a decrease in expression or activity of IDO1 in a biological sample from the subject compared to compared to just prior to administration of the inhibitor of IDO1 or compared to just prior to the initiation of administration of the T cell therapy;
an increase in the number of cells of the T cell therapy detectable in the blood from the subject compared to in the subject at a preceding time point just prior to administration of the inhibitor of IDO1 or compared to a preceding time point after administration of the T cell therapy;
the number of cells of the T cell therapy detectable in the blood being within 2.0-fold (greater or less) of the peak or maximum number of the cells of the T cell therapy detectable in the blood of the subject after the initiation of administration of the T cell therapy;
the number of cells of the T cell therapy detectable in the blood from the subject being greater than or greater than about 10%, 15%, 20%, 30%, 40%, 50%, or 60% of total peripheral blood mononuclear cells (PBMCs) in the blood of the subject;
the concentration or number of engineered cells in the blood of the subject being (i) at least at or about 10 engineered cells per microliter, (ii) at least 20%, 30%, 40% or 50% of the total number of peripheral blood mononuclear cells (PBMCs), (iii) at least or at least about 1×105 engineered cells; or (iv) the blood of the subject contains at least 5,000 copies of recombinant receptor-encoding DNA per micrograms DNA;
at day 90 following the initiation of the T cells, CAR-expressing cells are detectable in the blood or serum of the subject; or
at day 90 following the initiation of the T cells, the blood of the subject contains at least 20% CAR-expressing cells, at least 10 CAR-expressing cells per microliter or at least 1×104 CAR-expressing cells.