Mathematical Modeling of Immunotherapy for Tumors: Computational Analysis of Adoptive Cell Therapy with Interleukin-2
Autor(a) principal: | |
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Data de Publicação: | 2024 |
Outros Autores: | |
Tipo de documento: | Artigo |
Idioma: | por eng |
Título da fonte: | Revista Brasileira de Cancerologia (Online) |
Texto Completo: | https://rbc.inca.gov.br/index.php/revista/article/view/4446 |
Resumo: | Introduction: Cancer is one of the main causes of death in the world, but there are still unknown aspects of its dynamics. An important tool for its study is mathematical modeling, which analyzes and projects tumor behavior. A model must be validated in silico to be useful. Objective: Validate a mathematical model for immunotherapy against tumors, to evaluate how the cellular composition of the adoptive cell therapy interferes with the response and which is the most appropriate scheme for administering interleukin-2 in terms of dose and time of use. Method: An ordinary differential equation model was developed. The parameters were obtained from the literature, adapted or simulated. The solutions were found using Octave 8.1.0 software and compared with the literature. Results: The results, compared with data from clinical trials and other modeling, show that the model is valid for reproducing tumor dynamics. In addition, infusion of adoptive cell therapy with a predominance of CD8+ T lymphocytes appears slightly more advantageous than infusion with a predominance of CD4+ T lymphocytes; high but tolerable doses of interleukin-2 generate a better anti-tumor response; and longer administration of interleukin-2 maximizes the response. Conclusion: The model is valid for studying tumor dynamics and can help in the development of new research. In addition, immunotherapy with a predominance of CD8+ T lymphocytes over CD4+ T lymphocytes and with interleukin-2 in higher doses and for longer periods, respecting tolerance, showed better results in silico. |
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Mathematical Modeling of Immunotherapy for Tumors: Computational Analysis of Adoptive Cell Therapy with Interleukin-2Modelización Matemática de la Inmunoterapia de Tumores: Análisis Computacional de la Terapia Celular Adoptiva con Interleucina-2Modelagem Matemática da Imunoterapia para Tumores: Análise Computacional da Terapia Celular Adotiva com Interleucina-2Modelos TeóricosSimulação por ComputadorImunoterapia AdotivaNeoplasias/epidemiologiaModels, TheoreticalComputer SimulationImmunotherapy, AdoptiveNeoplasms/epidemiologyModelos TeóricosSimulación por ComputadorInmunoterapia AdoptivaNeoplasias/epidemiologíaIntroduction: Cancer is one of the main causes of death in the world, but there are still unknown aspects of its dynamics. An important tool for its study is mathematical modeling, which analyzes and projects tumor behavior. A model must be validated in silico to be useful. Objective: Validate a mathematical model for immunotherapy against tumors, to evaluate how the cellular composition of the adoptive cell therapy interferes with the response and which is the most appropriate scheme for administering interleukin-2 in terms of dose and time of use. Method: An ordinary differential equation model was developed. The parameters were obtained from the literature, adapted or simulated. The solutions were found using Octave 8.1.0 software and compared with the literature. Results: The results, compared with data from clinical trials and other modeling, show that the model is valid for reproducing tumor dynamics. In addition, infusion of adoptive cell therapy with a predominance of CD8+ T lymphocytes appears slightly more advantageous than infusion with a predominance of CD4+ T lymphocytes; high but tolerable doses of interleukin-2 generate a better anti-tumor response; and longer administration of interleukin-2 maximizes the response. Conclusion: The model is valid for studying tumor dynamics and can help in the development of new research. In addition, immunotherapy with a predominance of CD8+ T lymphocytes over CD4+ T lymphocytes and with interleukin-2 in higher doses and for longer periods, respecting tolerance, showed better results in silico.Introducción: El cáncer es una de las principales causas de muerte en todo el mundo, pero aún se desconocen aspectos de su dinámica. Una herramienta importante para su estudio es la modelización matemática, que analiza y proyecta el comportamiento tumoral. Para que un modelo sea útil debe ser validado in silico. Objetivo: Validar un modelo matemático de inmunoterapia contra tumores, evaluar cómo interfiere la composición celular de la terapia celular adoptiva en la respuesta y cuál es el esquema más adecuado de administración de interleuquina-2 en cuanto a dosis y tiempo de utilización. Método: Se desarrolló un modelo de ecuaciones diferenciales ordinarias. Los parámetros se obtuvieron de la literatura, se adaptaron o se simularon. Las soluciones se hallaron con el software Octave 8.1.0 y se compararon con las de la bibliografía. Resultados: Los resultados, comparados con datos de ensayos clínicos y otras modelizaciones, muestran que el modelo es válido para reproducir la dinámica tumoral. Además, la infusión de terapia celular adoptiva con predominio de linfocitos T CD8+ parece ligeramente más ventajosa que la infusión con predominio de linfocitos T CD4+; dosis altas pero tolerables de interleuquina-2 generan una mejor respuesta antitumoral; y la administración de interleuquina-2 durante más tiempo maximiza la respuesta. Conclusión: El modelo es válido para estudiar la dinámica tumoral y podría ayudar en el desarrollo de nuevas investigaciones. Además, la inmunoterapia con predominio de linfocitos T CD8+ sobre linfocitos T CD4+ y con interleuquina-2 en dosis más altas y durante más tiempo, respetando la tolerancia, mostró mejores resultados in silico.Introdução: O câncer é uma das principais causas de óbito no mundo, mas ainda há aspectos desconhecidos da sua dinâmica. Uma importante ferramenta para seu estudo é a modelagem matemática, que analisa e projeta o comportamento tumoral. Um modelo deve ser validado in silico para ser útil. Objetivo: Validar um modelo matemático para imunoterapia contra tumores, avaliar como a composição celular da terapia celular adotiva interfere na resposta e qual o esquema mais adequado para administração de interleucina-2 quanto à dose e ao tempo de uso. Método: Foi desenvolvido um modelo de equações diferenciais ordinárias. Os parâmetros foram obtidos da literatura, adaptados ou simulados. As soluções foram encontradas usando o software Octave 8.1.0 e comparadas com a literatura. Resultados: Os resultados, comparados com dados de ensaios clínicos e outras modelagens, mostram que o modelo é válido para reproduzir a dinâmica tumoral. Ademais, a infusão da terapia celular adotiva com predomínio de linfócitos T CD8+ parece ligeiramente mais vantajosa do que a infusão com predomínio de linfócitos T CD4+; doses altas, porém toleráveis, de interleucina-2 geram melhor resposta antitumoral; e a administração de interleucina-2 por mais tempo maximiza a resposta. Conclusão: O modelo é válido para estudo da dinâmica tumoral e pode auxiliar no desenvolvimento de novas pesquisas. Adicionalmente, a imunoterapia com predomínio de linfócitos T CD8+ em relação a linfócitos T CD4+ e com interleucina-2 em doses mais altas e por mais tempo, respeitando a tolerância, apresentou melhores resultados in silico.INCA2024-04-15info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArtigos, Avaliado pelos paresapplication/pdfapplication/pdfhttps://rbc.inca.gov.br/index.php/revista/article/view/444610.32635/2176-9745.RBC.2024v70n1.4446Revista Brasileira de Cancerologia; Vol. 70 No. 1 (2024): Jan./Feb./Mar.; e-164446Revista Brasileira de Cancerologia; Vol. 70 Núm. 1 (2024): ene./feb./mar.; e-164446Revista Brasileira de Cancerologia; v. 70 n. 1 (2024): jan./fev./mar.; e-1644462176-9745reponame:Revista Brasileira de Cancerologia (Online)instname:Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA)instacron:INCAporenghttps://rbc.inca.gov.br/index.php/revista/article/view/4446/3402https://rbc.inca.gov.br/index.php/revista/article/view/4446/3403Copyright (c) 2024 Revista Brasileira de Cancerologiahttps://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessAntunes, Jeferson Miguel Melo Rosa, Valéria Mattos da2024-04-15T17:47:31Zoai:rbc.inca.gov.br:article/4446Revistahttps://rbc.inca.gov.br/index.php/revistaPUBhttps://rbc.inca.gov.br/index.php/revista/oairbc@inca.gov.br0034-71162176-9745opendoar:2024-04-15T17:47:31Revista Brasileira de Cancerologia (Online) - Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA)false |
dc.title.none.fl_str_mv |
Mathematical Modeling of Immunotherapy for Tumors: Computational Analysis of Adoptive Cell Therapy with Interleukin-2 Modelización Matemática de la Inmunoterapia de Tumores: Análisis Computacional de la Terapia Celular Adoptiva con Interleucina-2 Modelagem Matemática da Imunoterapia para Tumores: Análise Computacional da Terapia Celular Adotiva com Interleucina-2 |
title |
Mathematical Modeling of Immunotherapy for Tumors: Computational Analysis of Adoptive Cell Therapy with Interleukin-2 |
spellingShingle |
Mathematical Modeling of Immunotherapy for Tumors: Computational Analysis of Adoptive Cell Therapy with Interleukin-2 Antunes, Jeferson Miguel Melo Modelos Teóricos Simulação por Computador Imunoterapia Adotiva Neoplasias/epidemiologia Models, Theoretical Computer Simulation Immunotherapy, Adoptive Neoplasms/epidemiology Modelos Teóricos Simulación por Computador Inmunoterapia Adoptiva Neoplasias/epidemiología |
title_short |
Mathematical Modeling of Immunotherapy for Tumors: Computational Analysis of Adoptive Cell Therapy with Interleukin-2 |
title_full |
Mathematical Modeling of Immunotherapy for Tumors: Computational Analysis of Adoptive Cell Therapy with Interleukin-2 |
title_fullStr |
Mathematical Modeling of Immunotherapy for Tumors: Computational Analysis of Adoptive Cell Therapy with Interleukin-2 |
title_full_unstemmed |
Mathematical Modeling of Immunotherapy for Tumors: Computational Analysis of Adoptive Cell Therapy with Interleukin-2 |
title_sort |
Mathematical Modeling of Immunotherapy for Tumors: Computational Analysis of Adoptive Cell Therapy with Interleukin-2 |
author |
Antunes, Jeferson Miguel Melo |
author_facet |
Antunes, Jeferson Miguel Melo Rosa, Valéria Mattos da |
author_role |
author |
author2 |
Rosa, Valéria Mattos da |
author2_role |
author |
dc.contributor.author.fl_str_mv |
Antunes, Jeferson Miguel Melo Rosa, Valéria Mattos da |
dc.subject.por.fl_str_mv |
Modelos Teóricos Simulação por Computador Imunoterapia Adotiva Neoplasias/epidemiologia Models, Theoretical Computer Simulation Immunotherapy, Adoptive Neoplasms/epidemiology Modelos Teóricos Simulación por Computador Inmunoterapia Adoptiva Neoplasias/epidemiología |
topic |
Modelos Teóricos Simulação por Computador Imunoterapia Adotiva Neoplasias/epidemiologia Models, Theoretical Computer Simulation Immunotherapy, Adoptive Neoplasms/epidemiology Modelos Teóricos Simulación por Computador Inmunoterapia Adoptiva Neoplasias/epidemiología |
description |
Introduction: Cancer is one of the main causes of death in the world, but there are still unknown aspects of its dynamics. An important tool for its study is mathematical modeling, which analyzes and projects tumor behavior. A model must be validated in silico to be useful. Objective: Validate a mathematical model for immunotherapy against tumors, to evaluate how the cellular composition of the adoptive cell therapy interferes with the response and which is the most appropriate scheme for administering interleukin-2 in terms of dose and time of use. Method: An ordinary differential equation model was developed. The parameters were obtained from the literature, adapted or simulated. The solutions were found using Octave 8.1.0 software and compared with the literature. Results: The results, compared with data from clinical trials and other modeling, show that the model is valid for reproducing tumor dynamics. In addition, infusion of adoptive cell therapy with a predominance of CD8+ T lymphocytes appears slightly more advantageous than infusion with a predominance of CD4+ T lymphocytes; high but tolerable doses of interleukin-2 generate a better anti-tumor response; and longer administration of interleukin-2 maximizes the response. Conclusion: The model is valid for studying tumor dynamics and can help in the development of new research. In addition, immunotherapy with a predominance of CD8+ T lymphocytes over CD4+ T lymphocytes and with interleukin-2 in higher doses and for longer periods, respecting tolerance, showed better results in silico. |
publishDate |
2024 |
dc.date.none.fl_str_mv |
2024-04-15 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Artigos, Avaliado pelos pares |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://rbc.inca.gov.br/index.php/revista/article/view/4446 10.32635/2176-9745.RBC.2024v70n1.4446 |
url |
https://rbc.inca.gov.br/index.php/revista/article/view/4446 |
identifier_str_mv |
10.32635/2176-9745.RBC.2024v70n1.4446 |
dc.language.iso.fl_str_mv |
por eng |
language |
por eng |
dc.relation.none.fl_str_mv |
https://rbc.inca.gov.br/index.php/revista/article/view/4446/3402 https://rbc.inca.gov.br/index.php/revista/article/view/4446/3403 |
dc.rights.driver.fl_str_mv |
Copyright (c) 2024 Revista Brasileira de Cancerologia https://creativecommons.org/licenses/by/4.0 info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Copyright (c) 2024 Revista Brasileira de Cancerologia https://creativecommons.org/licenses/by/4.0 |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
INCA |
publisher.none.fl_str_mv |
INCA |
dc.source.none.fl_str_mv |
Revista Brasileira de Cancerologia; Vol. 70 No. 1 (2024): Jan./Feb./Mar.; e-164446 Revista Brasileira de Cancerologia; Vol. 70 Núm. 1 (2024): ene./feb./mar.; e-164446 Revista Brasileira de Cancerologia; v. 70 n. 1 (2024): jan./fev./mar.; e-164446 2176-9745 reponame:Revista Brasileira de Cancerologia (Online) instname:Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA) instacron:INCA |
instname_str |
Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA) |
instacron_str |
INCA |
institution |
INCA |
reponame_str |
Revista Brasileira de Cancerologia (Online) |
collection |
Revista Brasileira de Cancerologia (Online) |
repository.name.fl_str_mv |
Revista Brasileira de Cancerologia (Online) - Instituto Nacional de Câncer José Alencar Gomes da Silva (INCA) |
repository.mail.fl_str_mv |
rbc@inca.gov.br |
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1797042241982693376 |