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US 12,761,213 B2Granted
Biomarker for transplantation tolerance induced by apoptotic donor leukocytes
AssigneeRegents of the University of Minnesota
InventorsBernhard J. Hering, Sabarinathan Ramachandran, Amar Singh
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Abstract
In certain embodiments, the present invention provides methods of identifying and treating a transplant recipient patient having transplantation tolerance induced by apoptotic donor leukocytes infused under cover of transient immunotherapy.
Claims19
A method of identifying a transplant recipient patient having long-term transplantation tolerance induced by one or more donor antigens administered under cover of transient immunotherapy, the method comprising:
- (a) assaying a first blood sample from the transplant recipient patient to detect a frequency of T regulatory Type 1 (Tr1) cells in the first blood sample, wherein the first blood sample is obtained pre-tolerization, pre-transplant, and pre-initiation of administration of a transient immunotherapy to the transplant recipient patient,
- (b) assaying a second blood sample from the transplant recipient patient to detect a frequency of T regulatory Type 1 (Tr1) cells in the second blood sample, wherein the second blood sample is obtained at least 28 days post-tolerization, post-transplant, and post-initiation of the administration of the transient immunotherapy;
- and
- (c) identifying the transplant recipient patient as having long-term transplantation tolerance induced by the one or more donor antigens when the frequency of Tr1 cells in the second blood sample is at least 2-fold greater than the frequency of Tr1 cells in the first blood sample,
- wherein the pre-tolerization comprises one or more donor antigens comprised in an apoptotic donor leukocyte (ADL) infusion,
- wherein the transient immunotherapy comprises at least one immunosuppressant, wherein the immunosuppressant is an inhibitor of CD40:CD40L co-stimulation, an mTOR inhibitor, or a concomitant anti-inflammatory therapy targeting proinflammatory cytokines, and wherein the effect of the transient immunotherapy is for 1 day to 12 months post-administration,
- wherein the T regulatory Type 1 (Tr1) cells express the markers CD49b+, LAG-3+, and CD4+,
- wherein the frequency of the Trl cells is a percentage of total CD4+ T cells in a blood sample, and
- wherein the long-term transplantation tolerance is for a period of time greater than one year.
6 more elements
A method, comprising:
- (a) obtaining a first blood sample from a transplant recipient patient to detect a baseline frequency of Tr1 cells in the first blood sample, wherein the first blood sample is obtained pre-tolerization, pre-transplant, and pre-initiation of transient immunotherapy;
- (b) obtaining a second blood sample from the transplant recipient patient to detect a frequency of Tr1 cells in the second blood sample, wherein the second blood sample is obtained at least 28 days post-tolerization, post-transplant, and post-initiation of administration of a transient immunotherapy to the transplant recipient patient;
- (c) assaying the first blood sample and the second blood sample to detect levels of Tr1 cells before and after tolerization, transplantation, and initiation of the administration of the transient immunotherapy to the transplant recipient patient;
- (d) identifying the transplant recipient patient as having transplantation tolerance induced by one or more donor antigens administered under cover of transient immunotherapy when the frequency of Trl cells in the second blood sample is at least 2-fold greater than the frequency of Trl cells in the first blood sample,
- wherein the pre-tolerization comprises one or more donor antigens comprised in an apoptotic donor leukocyte (ADL) infusion,
- wherein the transient immunotherapy comprises at least one immunosuppressant, wherein the immunosuppressant is an inhibitor of CD40:CD40L co-stimulation, an mTOR inhibitor, or a concomitant anti-inflammatory therapy targeting proinflammatory cytokines, and wherein the effect of the transient immunotherapy is for 1 day to 12 months post-administration,
- wherein the frequency of the Trl cells is a percentage of total CD4+ T cells in a blood sample, and
- wherein the T regulatory Type 1 (Tr1) cells express the markers CD49b+, LAG-3+, and CD4+.
5 more elements
Dependencies are inferred from the claim text.