Abstract 576P
Background
Although Immune checkpoint inhibitor (ICI) therapy usage has been increasing for various indications, some patients of various types of cancer were shown to not respond to ICI. To improve ICI response rate, a combination therapy targeting additional mechanisms to prevent tumour immune evasion by modulating the tumour microenvironment may be needed.
Methods
To investigate the enhanced anti-tumour effect of the anti-PD-1 antibody (aPD-1) with the addition of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG), the syngeneic model was used (n=6/group), LLC-1 lung carcinoma was implanted into the C57BL/6 mice subcutaneously. PLAG was daily administrated for 4 weeks with or without aPD-1 (RMP1-14). aPD-1 was delivered via IP injection once a week. The degree of infiltrated lymphocyte population and neutrophils in the tumour and blood on the sacrifice day were analyzed.
Results
In PLAG treated (50 or 100 mpk) mice group, the tumour burden was significantly reduced compared to a positive control (p < 0.05). In the group treated with aPD-1 alone, the tumour growth decreased by about 65% compared to the positive control. However, in mice co-treated with PLAG, the tumour was significantly reduced (18%) compared to the aPD-1 alone. The neutrophil-to-lymphocyte ratio levels in the group co-treated with PLAG were decreased remarkably compared to the aPD-1 alone. In particular, the degree of neutrophil infiltration in the tumour was effectively reduced upon PLAG treatment. Besides, the activity and infiltration of cytotoxic T-lymphocytes (CTLs) in the tumour were effectively increased in the group co-treated with PLAG compared to the aPD-1 alone. Such improvement was caused by a significant reduction of the population of Th17 which induced massive neutrophil infiltration in the tumour, compared to the positive control.
Conclusions
PLAG enhanced the anti-cancer effect of aPD-1 synergistically on the regression of tumour burden via decreasing the tumour-infiltrating neutrophils and Th17 population while increasing the CTLs. Therefore, combining aPD-1 with PLAG, which has excellent safety profiles, may contribute to enhancing the antitumor response of aPD-1 while lowering immune-related toxicities by reducing the dose of ICI.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Jae Wha Kim.
Funding
ENZYCHEM lifesciences.
Disclosure
All authors have declared no conflicts of interest.