通过靶向肿瘤相关巨噬细胞的嵌合受体工程化溶瘤病毒重振内源性抗肿瘤免疫
Rejuvenating endogenous antitumor immunity via a chimeric receptor-engineered oncolytic virus targeting tumor-associated macrophages.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Qualitative optimization of oncolytic virotherapy and immune therapy combination treatments.
Qualitative optimization of oncolytic virotherapy and immune therapy combination treatments.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
溶瘤病毒(OV)旨在选择性靶向并摧毁癌细胞,同时保护正常健康组织。目前有多种病毒正在开发用于溶瘤病毒治疗。本文将使用数学建模,考察提高溶瘤病毒治疗效果的关键策略,包括将免疫疗法与病毒治疗整合以增强抗肿瘤免疫应答,以及优化病毒给药时机、剂量和顺序。具体而言,我们考察提高病毒暴发量、调节免疫刺激和免疫抑制的策略,优化不同的每周病毒注射方案,并研究OV治疗与嵌合抗原受体(CAR)T细胞疗法的联合。数据可用性是模型的限制因素。我们采用多个不同数据集对模型进行参数化,但这些数据对应不同癌种和实验设计。因此,模型尚不能视为经过验证,所得结果属于定性结论。结果强调治疗时机对病毒疗法疗效和整体成功至关重要,并提出具有潜力的治疗情景,仍需未来通过实验进一步验证。
Oncolytic viruses (OVs) are designed to selectively target and destroy cancer cells while sparing normal, healthy tissue. Several viruses for oncolytic virotherapy are currently developed. In this paper, we will use mathematical modeling to consider key strategies that can improve the efficacy of oncolytic virotherapy. These include the integration of immunotherapy approaches with virotherapy to amplify anti-tumor immune responses, as well as optimizing the timing, dosage, and sequencing of viral administrations.
Specifically, we consider strategies that increase the burst size of the virus, immunostimulation and immunosuppression, we optimize for different weekly virus injection schedules, and we consider the combination of OV therapy with chimeric antigen receptor (CAR) T-cell therapy. A limiting factor is the availability of data.
We parametrize the model using several different data sets. These, however, correspond to different cancers and experimental setups. Hence our model cannot be considered to be validated. Consequently, our results are qualitative.
Our results highlight the critical importance of timing for virotherapy's efficacy and overall success. They outline strong evidence for promising treatment scenarios that needs to be further tested experimentally in the future.
MEMBER ACCOUNT
登录成功会直接打开下一页。