Single cell RNA-seq of Panc02-H7-Fluc model with vehicle tobemstomig, nivolumab and relatlimab-like treatment

We used transgenic mice challenged subcutaneously with Panc02-H7-Fluc tumors to compare the efficacy of tobemstomig with nivolumab and relatlimab-like monotherapies, as well as their combination, and further investigated their mechanism of action. We used a murinized version of tobemstomig, nivolumab and relatlimab-like anti-LAG-3 to prevent the formation of anti-drug antibodies and to prolong the treatment to 3 weeks. We performed single cell RNA sequencing on the tumor samples collected at day 28. We found both qualitative and quantitative differences between vehicle, mu-tobemstomig, mu-nivolumab monotherapy and in combination with mu-relatlimab-like anti-LAG-3.

本研究采用皮下接种Panc02-H7-Fluc肿瘤的转基因小鼠模型，对比托贝莫司汀（tobemstomig）、纳武利尤单抗（nivolumab）及类瑞莱利单抗抗LAG-3（anti-LAG-3）单药治疗的疗效，同时考察上述药物联合使用的治疗效果，并进一步探究各治疗方案的作用机制。本研究使用托贝莫司汀、纳武利尤单抗及类瑞莱利单抗抗LAG-3的鼠源化制剂，以避免抗药物抗体（anti-drug antibodies）的产生，并将治疗周期延长至3周。研究人员对第28天采集的肿瘤样本开展了单细胞RNA测序（single cell RNA sequencing）。研究发现，溶媒对照组、鼠源化托贝莫司汀（mu-tobemstomig）组、鼠源化纳武利尤单抗（mu-nivolumab）单药治疗组，以及联合鼠源化类瑞莱利单抗抗LAG-3的治疗组之间均存在质与量的差异。