Extracellular Vesicle Proteins And Their Use For Cancer Diagnosis, Predicting Response To Therapy, And Treatment
AssigneeThe Trustees of the University of Pennsylvania
InventorsXiaowei XU, Wei GUO, Gang CHEN
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Abstract
Compositions and methods are disclosed for treating cancer patients and identifying patients with a malignancy that are likely to respond to treatment with anti-PD-1/PD-L1 and other anti-cancer and immune-modulating therapeutics.
Claims21
1-32. (canceled)
A method of treating cancer in a subject identified as responsive to anti-cancer therapy, the method comprising
- i) determining the level of extracellular vesicle PD-L1 in a first biological sample obtained from the subject prior to treatment with an anti-cancer agent,
- ii) administering one or more anti-cancer agents to said subject,
- iii) determining the level of extracellular vesicle PD-L1 in a second biological sample obtained from the subject treated with said one or more anti-cancer agents,
- iv) identifying said subject as responsive to treatment where there is an increased level of extracellular vesicle PD-L1 in said second biological sample relative to said first biological sample, and
- v) administering an anti-cancer therapy directed to PD-1 and/or PD-L1 to said subject identified as responsive to treatment.
A method of treating cancer in a subject identified as responsive to anti-cancer therapy, the method comprising
- i) determining the level of extracellular vesicle PD-L1 in a biological sample obtained from the subject,
- ii) identifying said subject as responsive to treatment if the level of extracellular vesicle in the biological sample is below a reference level, and
- iii) administering an anti-cancer therapy directed to PD-1 and/or PD-L1 to said subject identified as responsive to treatment.
A method of detecting immune cell-derived protein containing vesicles or circulating PD-L1 containing vesicles in a biological sample obtained from a cancer patient, wherein the immune-cell derived protein containing vesicle is selected from the group consisting of immune cell derived protein containing exosomes, extracellular shedding vesicles, ectosomes, apoptotic bodies, and oncosomes, and wherein the circulating PD-L1 containing vesicle is selected from the group consisting of PD-L1 exosomes, extracellular shedding vesicles, ectosomes, apoptotic bodies, and oncosomes, the method comprising
- i) contacting said sample with a reagent or reagents that specifically bind said immune cell derived protein or a reagent that specifically binds PD-L1;
- and
- ii) detecting formation of a binding complex comprising said reagent or reagents bound to said immune cell derived protein containing vesicles or to said cancer derived PD-L1 containing vesicles, wherein said immune cell derived protein is selected from the group consisting of CD109, CD151, CD276, CD44, CD46, CD47, CD55, CD58, CD59, CD70, CD9, CD95, CD97, CD99, B7H4, CD3, CD4, CD8, CD11, CD14, CD16, CD19, CD20, CD24, CD25, CD27, CD38 CD45, CD68, CD80, CD86, CD138, CD152, CD160, CD223, CD244, CD274, CD276 and CD366.
Dependencies are inferred from the claim text.