Intraperitoneal oncolytic virotherapy for patients with malignant ascites: Characterization of clinical efficacy and antitumor immune response

Abstract

Oncolytic viruses mediate antitumor responses through direct tumor cell lysis and induction of host antitumor immunity. However, the therapeutic efficacy of oncolytic viruses against malignant ascites has rarely been explored. This study aimed to evaluate the efficacy, safety, and immunomodulatory effect of an intraperitoneal injection of human type 5 recombinant adenovirus (called H101) against malignant ascites. Forty patients with malignant ascites were recruited and treated with intraperitoneal H101 in the Fudan University Shanghai Cancer Center. The 4-week clinical responses were determined by an objective assessment of ascites volume change. The ascites response rate and ascites control rate were 40% (16/40) and 75% (30/40), respectively. The major adverse events following intraperitoneal H101 administration were mild-to-moderate abdominal pain (8/40, 20.0%) and fever (11/40, 27.5%); no grade III/IV adverse events were observed. Mass cytometry and immunocytological analysis at baseline, and days 7 and 14 post-treatment showed that intraperitoneally injected H101 led to marked tumor cell depletion, increased dendritic cell and CD8+ T cell densities. H101-meditated tumor-specific immune activation on day 14 post-treatment was further identified by enzyme-linked immunospot assay. In conclusion, intraperitoneal H101 administration was well tolerated and effective in treating malignant ascites; thus, its immune activation ability may be a promising tool in combination with immunotherapy.

Keywords

• malignant ascites
• oncolytic viruses
• mass cytometry
• antitumor immune response
• immunotherapy