Mathematical model of a personalized neoantigen cancer vaccine and the human immune system.
PLoS Comput Biol
; 17(9): e1009318, 2021 09.
Article
en En
| MEDLINE
| ID: mdl-34559809
ABSTRACT
Cancer vaccines are an important component of the cancer immunotherapy toolkit enhancing immune response to malignant cells by activating CD4+ and CD8+ T cells. Multiple successful clinical applications of cancer vaccines have shown good safety and efficacy. Despite the notable progress, significant challenges remain in obtaining consistent immune responses across heterogeneous patient populations, as well as various cancers. We present a mechanistic mathematical model describing key interactions of a personalized neoantigen cancer vaccine with an individual patient's immune system. Specifically, the model considers the vaccine concentration of tumor-specific antigen peptides and adjuvant, the patient's major histocompatibility complexes I and II copy numbers, tumor size, T cells, and antigen presenting cells. We parametrized the model using patient-specific data from a clinical study in which individualized cancer vaccines were used to treat six melanoma patients. Model simulations predicted both immune responses, represented by T cell counts, to the vaccine as well as clinical outcome (determined as change of tumor size). This model, although complex, can be used to describe, simulate, and predict the behavior of the human immune system to a personalized cancer vaccine.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Vacunas contra el Cáncer
/
Medicina de Precisión
/
Inmunoterapia
/
Melanoma
/
Modelos Teóricos
/
Antígenos de Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
PLoS Comput Biol
Asunto de la revista:
BIOLOGIA
/
INFORMATICA MEDICA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos