Howell Lars M, Forbes Neil S
Department of Chemical Engineering, University of Massachusetts, Amherst, MA 01003, USA.
Department of Microbiology, University of Massachusetts, Amherst, MA 01003, USA.
Bioengineering (Basel). 2025 Jul 10;12(7):751. doi: 10.3390/bioengineering12070751.
therapies are a promising tool for the treatment of solid tumors. can be engineered to increase their tumor infiltration, cell killing abilities, and immunostimulatory properties. However, bacterial therapies have often failed in clinical trials due to poor characterization. Mathematical models are useful for predicting the immune response to cancer treatments and characterizing the properties of bacterial invasion. Herein we develop an ordinary differential equation-based model that combines bacterial therapies with classical anti-tumor immunotherapies. Our modeling results suggest that increasing bacterial localization to the tumor is key for therapeutic efficacy; however, increased intracellular invasion and direct bacterial mediated cytotoxicity does not reduce tumor growth. Further, the model suggests that enhancing T cell-mediated cell death by both bacterial stimulation of pro-inflammatory cytokines and activation of T cells via antigen cascade is critical for therapeutic efficacy. A balance of intracellular and extracellular leads to more effective therapeutic response, which suggests a strategy for strain design to be tested in vivo. Overall, this model provides a system to predict which engineered features of therapies lead to effective treatment outcomes.
细菌疗法是治疗实体瘤的一种有前景的工具。可以对其进行改造以增强它们的肿瘤浸润、细胞杀伤能力和免疫刺激特性。然而，由于表征不佳，细菌疗法在临床试验中常常失败。数学模型有助于预测对癌症治疗的免疫反应并表征细菌侵袭的特性。在此，我们开发了一种基于常微分方程的模型，该模型将细菌疗法与经典抗肿瘤免疫疗法相结合。我们的建模结果表明，增加细菌在肿瘤中的定位是治疗效果的关键；然而，增加细胞内侵袭和直接细菌介导的细胞毒性并不能减少肿瘤生长。此外，该模型表明，通过促炎细胞因子的细菌刺激和通过抗原级联激活T细胞来增强T细胞介导的细胞死亡对治疗效果至关重要。细胞内和细胞外的平衡会导致更有效的治疗反应，这提示了一种在体内进行测试的菌株设计策略。总体而言，该模型提供了一个系统来预测细菌疗法的哪些工程特征会导致有效的治疗结果。
