Efficacy evaluation of chimeric antigen receptor-modified human peritoneal macrophages in the treatment of gastric cancer

BackgroundGastric cancer is one of the most common cancers. Peritoneal carcinomatosis (PC) appears to be the most common pattern of recurrence, and more than half of the GC patients eventually die from PC. Novel strategies for the management of patients with PC are urgently needed. Recently, rapid progress has been made in adoptive transfer therapy by using macrophages as the effector cells due to their capabilities of phagocytosis, antigen presentation, and high penetration. Here, we generated a novel macrophage-based therapy and investigated anti-tumoral effects on GC and potential toxicity.MethodsWe developed a novel Chimeric Antigen Receptor-Macrophage (CAR-M) based on genetically modifying human peritoneal macrophages (PMs), expressing a HER2-Fc & epsilon;R1 & gamma;-CAR (HF-CAR). We tested HF-CAR macrophages in a variety of GC models in vitro and in vivo.ResultsHF-CAR-PMs specifically targeted HER2-expressed GC, and harboured the Fc & epsilon;R1 & gamma; moieties to trigger engulfment. Intraperitoneal administration of HF-CAR-PMs significantly facilitated the HER2-positive tumour regression in PC mouse model and prolonged the overall survival rate. In addition, the combined use of oxaliplatin and HF-CAR-PMs exhibited significantly augment anti-tumour activity and survival benefit.ConclusionsHF-CAR-PMs could represent an exciting therapeutic option for patients with HER2-positive GC cancer, which should be tested in carefully designed clinical trials.

Automated summary

Researchers have developed a novel macrophage-based therapy for gastric cancer and investigated its anti-tumoral effects. The therapy specifically targeted HER2-expressed gastric cancer in vitro and in vivo. The combination of this therapy with oxaliplatin showed enhanced efficacy.