Ponente
Descripción
The term “cancer” encompasses a range of diseases characterized by uncontrolled cell proliferation and the potential to metastasize (National Cancer Institute (INCA), What Is Cancer?, Ministry of Health, 2023). Although widely used, traditional approaches such as chemotherapy, radiation therapy, and surgery face limitations, including systemic toxicity, low specificity, the development of tumor resistance, and side effects (Zafar, A. et al., Discov. Oncol. 16, Art. 607, 2025). Given these limitations, the combination of CAR-T cells with oncolytic viruses (OV) emerges as a promising alternative, combining specific recognition of tumor cells with selective infection and stimulation of the immune response (Fayyaz, A. et al., Discov. Oncol. 15, Art. 756, 2024; Rivera-Orellana, S. et al., Clin. Exp. Med. 25, Art. 256, 2025).
This study proposes a mathematical model based on ordinary differential equations to investigate the temporal interaction between populations of uninfected tumor cells ($T$), infected tumor cells ($T_{i}$), CAR-T cells ($C$), and oncolytic viruses ($V$). The mathematical model is given by
\begin{equation}
\begin{cases}
\frac{dT}{dt} = \alpha_1 T \left( 1 - \frac{T}{k_1} \right) - \mu_1 C T - \beta_1 T V, \
\frac{dT_i}{dt} = -\mu_2 C T_i + \beta_1 T V - \delta_2 T_i, \
\frac{dC}{dt} = C \left( \frac{\alpha_3 T}{k_3 + T} - \mu_3 T - \rho_3 \right), \
\frac{dV}{dt} = -\beta_1\lambda T V + b\delta_2 T_i - \alpha_4 V.
\end{cases}
\end{equation}
In the model, $\alpha_{1}$ and $k_{1}$ represent the growth rate and tumor carrying capacity, while $\mu_{1}$ and $\mu_{2}$ refer to the elimination of tumor cells by CAR-T cells. Viral dynamics are controlled by the infection rate $\beta_{1}$, lysis of infected cells $\delta_{2}$, viral production $b$, infection efficiency $\lambda$, and viral decay $\alpha_{4}$. For the immune response, the parameters $\alpha_{3}$, $k_{3}$, $\mu_{3}$, and $\rho_{3}$ describe, respectively, the activation, saturation, interaction, and mortality of CAR-T cells.
Qualitative analysis revealed four equilibrium points: total extinction $E_0=(0,0,0,0)$, exclusively tumor state $E_1=(k_1,0,0,0)$, and the tumor-CAR-T coexistence scenarios $ E_2=(T^*, 0,C^*,0)$ or tumor-virus $E_3 = (T^{**}, T_i^{**}, 0, V^{**})$. The stability of $E_{1}$ allowed us to identify thresholds for therapeutic success, associated with the basic viral reproduction number ($R_V$) and the immune system response. Preliminary results suggest that the virus acts transiently to reduce the initial tumor burden, potentially facilitating long-term control by CAR-T cells. Stability analysis of the remaining equilibria and numerical simulations are currently underway.