Posted: Friday, September 1, 2023
For patients with hepatocellular carcinoma, the use of a leukocyte-hitchhiking, dual-delivery liposomal platform to effectively administer immunotherapy may prove to be an effective strategy, according to a presentation given at the 2023 American Society of Clinical Oncology (ASCO) Breakthrough meeting (Abstract 168), in Yokohama, Japan. This study’s approach may pave the way for future clinical applications of immunotherapy for this patient population, suggested Yuejie Lu, MD, PhD, of the First Affiliated Hospital, Hangzhou, China, and colleagues.
Pyroptosis-inducing drugs were screened for efficacy using Western blot analysis. Co-delivery of small-molecule immunotherapy drugs and pyroptosis-inducing drugs was executed using the newly designed leukocyte-hitchhiking, liposome nanodrug delivery system. In vitro analyses were performed to evaluate whether the nanocarrier could effectively induce pyroptosis of liver cancer cells. In vivo evaluation of the nanocarrier’s ability to target peripheral blood leukocytes, as well as its role in tumor inhibition and immune activation, was performed.
The study findings revealed that gemcitabine successfully induced pyroptosis in liver cancer cells. Gemcitabine was co-delivered with the small-molecule PD-1/PD-L1 complex inhibitor BMS-202 using an E-selectin–modified liposome. Gemcitabine would evoke tumor cell pyroptosis, the investigators reported, whereas BMS-202 would inhibit the formation of the PD-1/PD-L1 complex. In vitro experiments revealed that the induction of pyroptosis in liver cancer cells and activation of immune cells were effective using the nanocarrier. Moreover, the nanocarrier successfully targeted leukocytes and inhibited the tumor cells while also activating the immune response.
Disclosure: The study authors reported no conflicts of interest.