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
67P - The effect of non-viral gene-immune therapy via OX40L or 4-1BBL on murine subcutaneous CT26 colon cancer model
Presenter: Olga Rakitina
Session: Poster session 09
68P - Dendritic polylysine with paclitaxel and triptolide codelivery for enhanced NSCLC ferroptosis through the accumulation of ROS
Presenter: Huae Xu
Session: Poster session 09
69P - Novel monoclonal antibodies can distinguish Cripto-1 from Cripto-3 proteins: Clinical implications and potential new biomarkers
Presenter: Josune Garcia-Sanmartin
Session: Poster session 09
70P - The human intratumor mycobiome is significantly influenced by an individual's race
Presenter: Dan Coster
Session: Poster session 09
71P - Preclinical characterization of ARX305: A next-generation anti-CD70 antibody drug conjugate for the treatment of CD70-expressing cancers
Presenter: Lillian Skidmore
Session: Poster session 09
72P - Impact of extended panel of genes for germline cancer testing
Presenter: Shaheenah Dawood
Session: Poster session 09
73P - Preclinical and clinical presentation of the nerve-driven tumor spread
Presenter: Dawid Sigorski
Session: Poster session 09
74P - Characterization of ERBB2 variation and their association with immune response in solid tumours
Presenter: Dong Wang
Session: Poster session 09
76P - Improvement of whole-cell cancer vaccine anti-tumor effect by different injection methods
Presenter: Chin yang Chang
Session: Poster session 09
77P - Normative data on the sexual health questionnaires - QLQ-SHQ22, and the sexual domains of the QLQ-BR23/BR45 - for Norwegian general population with and without cancer
Presenter: Ragnhild Åsberg
Session: Poster session 09