A minimal model of T cell avidity may identify subtherapeutic vaccine schedules
| Autor: | Peter P. Lee, Danya Rose, Adarsh Kumbhari, Peter S. Kim |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Statistics and Probability medicine.medical_treatment T cell T-Lymphocytes chemical and pharmacologic phenomena Biology Cancer Vaccines Models Biological General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Immune system Antigen Clinical history Neoplasms medicine Humans Avidity Immunization Schedule General Immunology and Microbiology Applied Mathematics Cancer General Medicine Immunotherapy medicine.disease 030104 developmental biology medicine.anatomical_structure Multiple factors Modeling and Simulation Cancer cell Immunology General Agricultural and Biological Sciences 030215 immunology |
| Zdroj: | Mathematical biosciences. 334 |
| ISSN: | 1879-3134 |
| Popis: | T cells protect the body from cancer by recognising tumour-associated antigens. Recognising these antigens depends on multiple factors, one of which is T cell avidity, i.e., the total interaction strength between a T cell and a cancer cell. While both high- and low-avidity T cells can kill cancer cells, durable anti-cancer immune responses require the selection of high-avidity T cells. Previous experimentation with anti-cancer vaccines, however, has shown that most vaccines elicit low-avidity T cells. Optimising vaccine schedules may remedy this by preferentially selecting high-avidity T cells. Here, we use mathematical modelling to develop a simple, phenomenological model of avidity selection that may identify vaccine schedules that disproportionately favour low-avidity T cells. We calibrate our model to our prior, more complex model, and then validate it against several experimental data sets. We find that the sensitivity of the model’s parameters change with vaccine dosage, which allows us to use a patient’s data and clinical history to screen for suitable vaccine strategies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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