Methods of predicting and treating immunotherapy adverse events based on immune cell populations
AssigneeBoard of Regents, The University of Texas System
InventorsDavid E. GERBER, John David FARRAR, Hong MU-MOSLEY, Jason Y. PARK
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Abstract
The present disclosure generally relates to compositions and methods for predicting or diagnosing immune-related adverse events (irAE) before, during, or after immune checkpoint inhibitor (ICI) treatment in a subject with cancer. The method includes assessment of abundance or expression of immune cells, autoantibodies, and/or cytokines.
Claims41
A method of predicting and/or monitoring the risk of developing and/or diagnosing immune-related adverse events (irAE) associated with immune checkpoint inhibitor (ICI) treatment in a subject comprising:
- a) providing a sample from the subject;
- b) assessing immune cell subset in the sample, wherein the assessment comprises determining the abundance of one or more immune cell subsets in the sample;
- and
- c) predicting risk for developing/diagnosing irAE in the subject wherein, the subject is predicted as having a high risk of developing or diagnosed with having irAE if the abundance of one or more immune cell subsets CD57hi CD56− TE CD8 T cells, CD57lo CD56− TE CD8 T cells, naïve B cells, naïve CD4 T cells, CD57hi CD56+TE CD8 T cells, memory B cells, EM CD8 T cells, CD57lo CD56+TE CD8 T cell, naïve CD8 T cells, gamma delta T cells, pDC, plasmablasts, CTLA-4+ naïve B cells, or any combination thereof are different in the subject when compared to the abundance of the one or more immune cell subsets in a control sample.
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A method of treating a subject with cancer comprising:
- (a) providing a sample from the subject;
- (b) assessing immune cell subset in the sample, wherein the assessment comprises determining the abundance of one or more of immune cell subsets in CD57hi CD56− TE CD8 T cells, CD57lo CD56− TE CD8 T cells, naïve B cells, naïve CD4 T cells, CD57hi CD56+TE CD8 T cells, memory B cells, EM CD8 T cells, CD57lo CD56+TE CD8 T cell, naïve CD8 T cells, gamma delta T cells, pDC, plasmablasts, CTLA-4+ naïve B cells, or any combination thereof in the sample;
- (c) diagnosing the subject's risk of developing irAE, wherein the subject is diagnosed as:
- (i) high risk when the abundance of one or more of naïve B cells, CD57hiCD56+TE CD8 T cells, memory B cells, gamma delta T cells, naïve CD8 T cells, naïve CD4 T cells, or any combination thereof are lower in the sample from the subject compared to the abundance in a control sample;
- (ii) low risk of developing irAE if the abundance of one or more of naïve B cells, CD57hiCD56+TE CD8 T cells, memory B cells, gamma delta T cells, naïve CD8 T cells, naïve CD4 T cells, or any combination thereof elevated in the sample from the subject compared to the abundance in a control sample;
- (ii) low risk when the abundance of one or more of CD57lo CD56− terminal effector CD8 cells, CD57hi CD56-terminal effector CD8 T cells, EM CD8 T cells, plasmacytoid dendritic cells, plasmablasts, CLTA-4+ naïve B cells, or any combination thereof are lower or equal in the sample from the subject when compared to the abundance in a control sample;
- and/or
- (iii) high risk when the abundance of one or more of CD57lo CD56− terminal effector CD8 cells, CD57hi CD56-terminal effector CD8 T cells, EM CD8 T cells, plasmacytoid dendritic cells, plasmablasts, CLTA-4+ naïve B cells, or any combination thereof are greater in the sample from the subject when compared to abundance in a control sample;
- (d) treating the subject with:
- (i) an ICI therapy if subject is diagnosed as low risk of developing irAE;
- (ii) a non-ICI therapy if the subject is diagnosed as high risk of developing irAE;
- or
- (iii) an ICI therapy and an irAE mitigating therapy if the subject is diagnosed as high risk of developing irAE.
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A method of identifying the presence of at least one differentially expressed immune cell subset associated with irAE in a biological sample of a subject with cancer, the method comprising:
- a. providing a biological sample from the subject;
- b. assessing immune cells in the sample, wherein the assessment comprises detecting the abundance of one or more immune cell subsets disclosed in CD57hi CD56− TE CD8 T cells, CD57lo CD56− TE CD8 T cells, naïve B cells, naïve CD4 T cells, CD57hi CD56+TE CD8 T cells, memory B cells, EM CD8 T cells, CD57lo CD56+TE CD8 T cell, naïve CD8 T cells, gamma delta T cells, pDC, plasmablasts, CTLA-4+ naïve B cells, or any combination thereof;
- and
- c. comparing the abundance of one or more immune cell subsets to the abundance in a control sample to identify the presence of differentially expressed immune cell subset(s);
- wherein the subject is planning, undergoing, or has completed immune checkpoint inhibitor (ICI) treatment.
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Dependencies are inferred from the claim text.