Methods to specifically profile protease activity at lymph nodes
AssigneeMassachusetts Institute of Technology
InventorsSangeeta N. Bhatia, Darrell J. Irvine, Karl Dane Wittrup, Andrew David Warren, Jaideep S. Dudani, Naveen K. Mehta
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Abstract
In some aspects, the disclosure provides compositions and methods for detecting and monitoring the activity of pro teases in vivo using affinity assays. The disclosure relates, in part, to the discovery that biomarker nanoparticles targeted to the lymph nodes of a subject are useful for the diagnosis and monitoring of certain medical conditions (e.g., metastatic cancer, infection with certain pathogenic agents).
Claims16
A composition for detecting the activity of a granzyme present in a lymph node, comprising:
- a lymph node biomarker nanoparticle, wherein the lymph node biomarker nanoparticle comprises a modular structure having a carrier domain comprising a lymph node trafficking carrier linked via a substrate for the granzyme to a detectable marker, wherein the lymph node trafficking carrier accumulates more of the lymph node biomarker nanoparticle in the lymph node of a subject as compared to the subject's liver, whereby when the biomarker nanoparticle is exposed to the granzyme in the lymph node in the subject, the detectable marker is released from the carrier domain, enters the subject's bloodstream, is excreted in urine from the subject, and is detectable ex vivo in the urine.
A composition for detecting the activity of a granzyme present in a lymph node, comprising:
- a lymph node biomarker nanoparticle comprising a lymph node trafficking carrier domain linked via a granzyme substrate to a detectable marker that, when the biomarker nanoparticle is exposed to the granzyme in the lymph node in a subject, said detectable marker is released from the carrier domain, enters the subject's reticuloendothelial system, is excreted in urine from the subject, and is detectable ex vivo in the urine and wherein the lymph node trafficking carrier domain accumulates more of the lymph node biomarker nanoparticle in the lymph node of a subject as compared to the subject's liver.
A composition comprising:
- a lymph node biomarker nanoparticle, wherein the lymph node biomarker nanoparticle comprises a modular structure having a carrier domain comprising a lymph node trafficking carrier linked to an enzyme susceptible detectable marker, wherein the lymph node trafficking carrier accumulates more of the lymph node biomarker nanoparticle in a lymph node of a subject as compared to the subject's liver, wherein the enzyme susceptible detectable marker is comprised of a substrate for a granzyme linked to a detectable marker whereby when the biomarker nanoparticle is exposed to the granzyme at the lymph node in the subject, the detectable marker is released from the biomarker nanoparticle, enters the subject's bloodstream, is excreted in urine from the subject, and is detectable ex vivo in the urine, wherein substrate for the granzyme comprises SEQ ID NO:
- 71, SEQ ID NO:
- 72, or SEQ ID NO:
- 73.
A composition comprising:
- a lymph node biomarker nanoparticle comprising a lymph node trafficking carrier domain linked via a granzyme substrate to a detectable marker that, when the biomarker nanoparticle is exposed to the granzyme at a lymph node in a subject, is released from the carrier domain, enters the subject's reticuloendothelial system, is excreted in urine from the subject, and is detectable ex vivo in the urine and wherein the lymph node trafficking carrier domain accumulates more of the lymph node biomarker nanoparticle in the lymph node of the subject as compared to the subject's liver, wherein granzyme substrate comprises SEQ ID NO:
- 71, SEQ ID NO:
- 72, or SEQ ID NO:
- 73.
Dependencies are inferred from the claim text.