Abstract 75P
Background
Cancer immunotherapy is dependent on immunostimulation to reorganise the tumour microenvironment (TME) and to increase anti-tumour effects of immune cells. There are currently many immunostimulants applicable to cancer therapy, such as antibodies, molecular drugs and PAMP activators. Choice of immunostimulant may be key, but method of delivery of treatment is equally as important as different routes may stimulate different immune pathways. Despite of the rapid development of nucleic acid drugs in recent years, the effect of nucleic acid on tumor immunity needs to be further investigated. Polyinosinic:polycytidylic acid (poly I:C) is a synthetic double-stranded RNA analog that shows promise as an adjuvant in cancer vaccines or immunotherapies. Poly I:C is known to interact with Toll-like receptor 3 (TLR3) when taken up by endocytosis, but when directly transfected into cells, poly I:C stimulates retinoic acid-inducible gene I (RIG-I) instead.
Methods
Poly I:C was used to mimic anti-tumour response after nucleic acid administration. Murine 4T1 mammary tumour-bearing BALB/c mice were treated with poly I:C by electroporation (EP) or syringe injection (SI) and monitored for tumour growth. To determine whether poly I:C-activated immune pathways differed between delivery modes, RIG-I and TLR3 pathway inhibitors were used to inhibit poly I:C-induced anti-tumour effect in 4T1 tumour model.
Results
Our results showed that poly I:C EP treatment induced stronger tumour suppression effect and tumour-specific adaptive immune response than via SI. And that this EP-treated anti-tumour effect could be suppressed by both RIG-I and TLR3 pathway inhibitors, but not in SI, suggesting that treatment of poly I:C via different delivery modes do activate different immune pathways.
Conclusions
We have demonstrated that poly I:C could induce different anti-tumour effects dependent on treatment delivery method. Our results suggest that the effects of nucleic acid drugs may vary depending on how they are administered.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Osaka University.
Funding
Osaka University.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
14P - Peripheral immune kinetics in survival prediction of small cell lung cancer patients treated with immune checkpoint blockade therapy
Presenter: MIGUEL GALINDO CAMPOS
Session: Poster session 09
15P - CBL E3 ubiquitin ligases are key inhibitory regulators in PD-1/LAG-3 co-signaling in human cancers, targeted through bispecific co-blockade
Presenter: Luisa Chocarro
Session: Poster session 09
16P - Terminally exhausted CD8+ T cells and increased immunosuppressive soluble factors in malignant ascites of patients with gastric cancer with peritoneal metastasis
Presenter: Hye Sook Han
Session: Poster session 09
17P - Continued expansion of long-lived effect CD8+ T cells associates with durable response post-PD-1 blockade
Presenter: Robert Watson
Session: Poster session 09
18P - Exposure of calreticulin is required for vitamin C immunomediated cancer surveillance
Presenter: Alessandro Cavaliere
Session: Poster session 09
19P - Preclinical and clinical significance of VEGF deprivation in ovarian cancer through a specific active immunotherapy
Presenter: Yanelys Morera
Session: Poster session 09
20P - The essential role of DNA repair in the pharmacological activities of AST-3424
Presenter: Fanying Meng
Session: Poster session 09
21P - Implications of KMT2C knockdown for DNA damage repair in breast cancer
Presenter: Philip Bredin
Session: Poster session 09
22P - Clinical significance of DNA damage response mutations in early stage NSCLC
Presenter: Haoran Zhang
Session: Poster session 09
23P - PMC-309: A highly selective anti-VISTA antibody reverses immunosuppressive TME to immune-supportive
Presenter: Cheon Ho Park
Session: Poster session 09