Mathematical Model of a Personalized Neoantigen Cancer Vaccine and the Human Immune System: Evaluation of Efficacy

AbstractCancer 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 as a proof of concept 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 recent 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). These kinds of models have the potential to lay the foundation for generating in silico clinical trial data and aid the development and efficacy assessment of personalized cancer vaccines.Author summaryPersonalized cancer vaccines have gained attention in recent years due to the advances in sequencing techniques that have facilitated the identification of multiple tumor-specific mutations. This type of individualized immunotherapy has the potential to be specific, efficacious, and safe since it induces an immune response to protein targets not found on normal cells. This work focuses on understanding and analyzing important mechanisms involved in the activity of personalized cancer vaccines using a mechanistic mathematical model. This model describes the interactions of a personalized neoantigen peptide cancer vaccine, the human immune system and tumor cells operating at the molecular and cellular level. The molecular level captures the processing and presentation of neoantigens by dendritic cells to the T cells using cell surface proteins. The cellular level describes the differentiation of dendritic cells due to peptides and adjuvant concentrations in the vaccine, activation, and proliferation of T cells in response to treatment, and tumor growth. The model captures immune response behavior to a vaccine associated with patient specific factors (e.g., different initial tumor burdens). Our model serves as a proof of concept displaying its utility in clinical outcomes prediction, lays foundation for developing in silico clinical trials, and aids in the efficacy assessment of personalized vaccines.