Kinase Activity Profiling for Predicting ICI Treatment Response
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Solution Overview
Problem
Current immune checkpoint inhibitors (ICIs) for treating cancer, such as PD-1 and PD-L1 inhibitors, have variable efficacy and can cause severe adverse effects, necessitating the development of predictive biomarkers to determine patient response before treatment initiation.
Innovation Solution
Measuring kinase activity in blood samples using protein kinase substrates to generate phosphorylation profiles, focusing on kinases from specific families like VEGFR, PDGFR, SRC, SYK, TAM, JakA, and ALK, to predict patient response to PD-1 or PD-L1 ICIs, independent of the underlying neoplastic disease.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune checkpoint inhibitors are used to treat cancer patients, then antitumor immune responses are reinvigorated, but durable responses are only obtained in a minority of patients and severe immune-related adverse events occur
Solution Approach 1:
The patent applies preliminary action by measuring kinase activity in blood samples before initiating ICI therapy to predict treatment response. This pre-treatment assessment allows clinicians to identify patients likely to respond durably versus those at risk of adverse events or primary resistance, enabling informed treatment decisions before exposure to potentially harmful ICIs.
Solution Approach 2:
The patent uses kinase activity measurement as an intermediary biomarker to mediate between the administration of ICI therapy and the prediction of clinical outcomes. Rather than directly observing tumor response or adverse events, the kinase activity profile serves as an intermediate indicator that predicts treatment efficacy and safety, allowing indirect assessment of ICI impact.
2Measurement precision
If kinase activity measurement is performed using multiple kinase families to predict ICI response, then prediction accuracy is improved, but measurement complexity increases
Solution Approach 1:
The patent applies universality by using a single blood sample analysis system that simultaneously measures kinase activity across multiple kinase families (VEGFR, PDGFR, SRC, SYK, TAM, JakA, ALK). This multi-functional approach allows one measurement platform to assess predictive information from multiple kinase pathways, improving prediction accuracy without requiring separate assays for each kinase family.
Solution Approach 2:
The patent applies parameter changes by measuring the activity state of kinases in blood samples, where the kinase activity level serves as the critical parameter. By quantifying phosphorylation levels or enzymatic activity of kinases from different families, the system translates complex molecular information into measurable parameters that predict ICI response, transforming biological complexity into quantifiable predictive data.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This method allows for early determination of the most suitable treatment and predicts patient response to PD-1 or PD-L1 ICIs, improving treatment efficacy and minimizing adverse effects by identifying kinase activity profiles that correlate with treatment outcomes in various cancers like melanoma, lung cancer, and bladder cancer.
Implementation Method 1
contacting the blood sample from the patient with one or more kinase substrate(s), preferably protein kinase substrate(s), thereby generating one or more phosphorylation profile(s)
Data Source
AI summary
The present invention provides methods for predicting the response of a patient in need of an immune checkpoint inhibitor (ICI), to treatment with a programmed cell death-1 (PD-1) or programmed death-ligand 1 (PD-L1) ICI, comprising the steps of: (a) measuring the kinase activity of at least two kinases independently selected from within at least two families of kinases selected from the group consisting of: the VEGFR or PDGFR family of kinases; the SRC family of kinases; the SYK family of kinases; the TAM family of kinases; the JakA family of kinases; and the ALK family of kinases, in a blood sample obtained from said patient, thereby providing a kinase activity profile of said blood sample; and (b) predicting from said kinase activity profile the response of said patient to treatment with said PD-1 or PD-L1 ICI, and kits for predicting the response of a patient in need of an ICI to treatment with a PD-1 or PD-L1 ICI.