Treatment of cancer utilizing an identified adenosine fingerprint
Inventors
Anderson, Amy Elizabeth • Ashok, Devika • DiRenzo, Daniel M. • Udyavar, Akshata R. • Walters, Matthew J. • Young, Stephen W.
Assignees
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Publication Number
US-12310965-B2
Publication Date
2025-05-27
Expiration Date
Abstract
The present disclosure provides methods of treating a cancer in a subject having an established adenosine fingerprint. An established adenosine fingerprint includes assessing the blood concentration of one or more adenosine machinery proteins, assessing the enzymatic activity of one or more adenosine machinery proteins, and/or assessing the tumor expression level of adenosine machinery proteins. The methods disclosed herein include administering to said subjects a therapeutic agent selected from the group consisting of an agent targeting the extracellular production of adenosine, and an agent antagonizing the activation by adenosine of one of its receptors.
Core Innovation
The invention relates to inhibiting or suppressing a cancer in a subject in need thereof by administering a therapeutically effective amount of a CD73 inhibitor, wherein the cancer has an established adenosine fingerprint determined from a biopsy from the subject. The established adenosine fingerprint is defined by an increase in the amount of CD73 as determined by immunostaining for CD73, thereby linking therapeutic CD73 inhibition to a biomarker pattern in the subject's biopsy.
The invention further specifies quantitative criteria for defining the established adenosine fingerprint. The increase in the amount of CD73 as determined by immunostaining is a measured value above a threshold value, where the threshold corresponds to a CD73 staining of 1% or more of cancer cells in the biopsy, or a measured value above an average value of CD73 immunostaining in biopsy samples from a population of subjects with the same type of cancer.
The disclosure further frames the overall strategy in terms of extracellular adenosine production and adenosine receptor antagonists as part of therapeutic options, and it includes combinations and kits as contemplated uses. The disclosure also includes characterization concepts for the fingerprint, including immunostaining and mRNA-level upregulation, and discusses combinations with agents such as PD-1/PD-L1 inhibitors and chemotherapeutic agents in certain refinements.
Claims Coverage
The independent claims cover treatment of cancer based on a biopsy-determined adenosine fingerprint characterized by increased CD73 immunostaining, followed by administration of a CD73 inhibitor identified as Compound A. The inventive features center on the CD73-based fingerprint definition and the use of Compound A as the therapeutic agent.
Biopsy-determined adenosine fingerprint with CD73 immunostaining increase
A method of inhibiting or suppressing a cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a CD73 inhibitor, wherein the cancer has an established adenosine fingerprint determined from a biopsy from the subject, and wherein the established adenosine fingerprint is an increase in the amount of CD73 as determined by immunostaining for CD73.
Threshold or population-average CD73 immunostaining qualification
The method wherein the increase in the amount of CD73 as determined by immunostaining is a measured value above a threshold value that is a CD73 staining of 1% or more of cancer cells in the biopsy or a measured value above an average value of CD73 immunostaining in biopsy samples from a population of subjects with the same type of cancer.
Compound A administration for inhibiting or suppressing cancer
administering to the subject a therapeutically effective amount of a CD73 inhibitor, wherein the CD73 inhibitor is Compound A or a pharmaceutically acceptable salt thereof.
The claims are directed to treating cancer by administering Compound A, a CD73 inhibitor, to a subject whose biopsy establishes an adenosine fingerprint characterized by increased CD73 immunostaining, quantified either by a 1% staining threshold for cancer cells or by exceeding an average CD73 immunostaining level in a comparable population. Dependent claims refine the immunostaining quantification and optionally add combination therapy and additional therapeutic agents.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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