Method and system for assessing immune system response
Inactive Publication Date: 2010-12-16
IMMUNEERING CORP
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Benefits of technology
[0017]One aspect of the invention involves extending the model of receptor-ligand binding and trafficking to cells that are NOT cytotoxic immune system cells, but that compete with cytotoxic immune cells for particular ligands. The number of receptor-ligand surface complexes on a cytotoxic immune cell depends significantly on the quantity of ligand available. Other cell types besides cytotoxic immune cells can influence the quantity of ligand available and thus influence the development of a cytotoxic reaction. Receptor-ligand binding and trafficking dynamics are equally important for these other cell types, and so a model of receptor-ligand binding on these other cell types can provide vital information for analyzing cytotoxicity.
[0018]One aspect of the invention involves modeling the dynamics or one or more receptor types on regulatory T cells (CD4+CD25+foxp3 Tregs) in addition to natural killer (NK) cells or cytotoxic T lymphocytes. In one specific embodiment, the model includes the IL-2 receptor and is able to capture the “competition” between Tregs and NK cells for a limited supply of a ligand which in this case is IL-2. Tregs deplete the concentration of IL-2 and reduce the amount available for NK cells. In another embodiment, the dynamics of the TGFβ receptor are modeled for malignant cells in addition to NK cells. In this embodiment, the model is able to capture the fact that as tumors reduce their expression of TGBβ receptors, more is available to bind to NK cells and inhibit the NK cells from developing a cytotoxic response.
Problems solved by technology
Fewer than 25% of patients respond to a typical cancer therapy, and there is usually no way to identify likely responders before treatment is administered.
Many therapeutic regimens that are lifesaving for particular subpopulations of patients fail to gain government approval due to low response rates in the general population.
This deprives patients of lifesaving therapies and causes significant financial losses for pharmaceutical and biotechnology companies.
During the months required to assess response to a therapy, patients may die or be so severely weakened that another therapy cannot be attempted.
As a result, health plans waste tens of thousands of dollars per patient on ineffective treatments.
High-dose IL-2 treatment is so toxic that patients must be hospitalized in intensive care, costing payers $60,000 per cycle of therapy.
This toxicity and the low response rate leads some patients to forgo IL-2 therapy, opting instead for therapies that are less toxic but that cannot provide a complete response.
However, there is currently no effective means for identifying those likely responders.
As a result clinical trials in the general melanoma population have produced relatively minor improvements in median survival time, leading the manufacturer to cancel a Phase III tremelimumab trial at great financial loss.
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[0023]Aspects of the invention are described below with reference to illustrative embodiments. However, aspects of the invention are not limited to the embodiments described.
[0024]As described above, aspects of the invention provide techniques for assessing the likely response of a patient's immune system to one or more therapeutic regimens. As used herein, a therapeutic regimen may involve a treatment that is performed one or more times for a patient, and the treatment may involve the use of one or more drugs or compounds, the use of electromagnetic or other radiation, the use of physical touch or other manipulation or alteration of patient body portions (such as surgery to implant a tissue or device, or to remove tissue or a device), and so on. In short, a therapeutic regimen may include any suitable technique or procedure used to treat a disease or other patient condition.
[0025]The assessment of the immune system response may be performed based on a set of values for measurable para
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A method and system for determining the extent to which a patient will respond to a therapeutic regimen by assessing how that regimen will impact the functioning of a patient's immune system. An extent to which a patient will respond to a therapeutic regimen may be assessed based on a set of values for measurable parameters that relate to one or more characteristics of the patient's immune system, and receptor-ligand binding and trafficking characteristics of the patient's immune system, as well as other optional parameters and characteristics of the immune system. A mathematical model of the immune system is provided and may be implemented to predict immune system response, as well as identify parameters that have a greatest impact on predicting immune system response.
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