Abstract 4079
Background
Glioblastoma (GBM) employs a variety of mechanisms to suppress the tumour immune microenvironment. A therapeutic approach aiming to abolish immunosuppressive cells and activate anti-GBM immunity would provide a powerful treatment strategy against GBM. We investigated whether photoimmunotherapy (PIT) targeting epidermal growth factor receptor (EGFR) can promoteT cell activation, whilst overcoming the immunologically cold status of GBM.
Methods
The phthalocyanine dye (IR700) was conjugated to affibody molecule (ZEGFR:03115). Cell viability, reactive oxygen species (ROS) production and major damage associated molecular patterns (calreticulin (CRT), heat shock protein 70 (Hsp70), high mobility group box 1 (HMGB1), and ATP) were studied in human and murine glioma cell lines post-ZEGFR:03115–IR700 PIT using flow cytometry (FC), Western blot and ELISA. Maturation of dendritic cells (DCs) stimulated by ZEGFR:03115-IR700 PIT was verified by FC. Xenografts and syngeneic murine tumour models (subcutaneous and orthotopic) were used to determine therapeutic and tumour-specific immune response following PIT. Post-treatment tumours were evaluated ex vivo.
Results
Cells treated with ZEGFR:03115–IR700 PIT showed a significant decrease in cell viability. Generation of ROS post-PIT resulted in translocation of CRT to the cell membrane and the release of HMGB1, Hsp70 and ATP. FC analysis showed significant increase in the surface expression of CD86 and HLA-DR molecules on DCs stimulated by ZEGFR:03115–IR700 PIT compared to the negative controls. In vivo, PIT led to a significant delay in subcutaneous tumour growth. A therapeutic efficacy of the conjugate was observed in brain tumours as early as 24 h post-irradiation. Ki-67, CD31, H&E staining of tumour sections showed a reduced cell proliferation index, distinct differences in vessel density, extensive tumour necrosis and microhaemorrhage on the margins of the treated tumours. In addition, tumour-infiltrating lymphocytes were elevated in the treated mice compared with the controls.
Conclusions
EGFR-targeted PIT is an attractive therapeutic strategy that boosts the anti-tumour T cell response which might influence the suppressed immune microenvironment in GBM patients.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The Institute of Cancer Research; The National Science Centre (NCNOPUS13#2017/25/B/NZ5/00039); and CRUK Convergence Science Centre Fund.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5939 - Matrix metalloproteinases and their tissue inhibitors genes abnormal DNA methylation in breast cancer
Presenter: Olga Simonova
Session: Poster Display session 1
Resources:
Abstract
2703 - Uveal melanoma cell lines depend on multiple signaling pathways for survival
Presenter: John Park
Session: Poster Display session 1
Resources:
Abstract
4849 - XAF1 and ZNF313 complex stimulates ER stress-induced apoptosis via direct GRP78 inhibition.
Presenter: Sungchan Jang
Session: Poster Display session 1
Resources:
Abstract
4801 - XAF1 assembles a destructive complex to induce BRCA1-mediated apoptosis via suppressing ERa and switching estrogen function
Presenter: Seung-hun Jang
Session: Poster Display session 1
Resources:
Abstract
3416 - Cancer associated fibroblasts promote cancer progression via Wnt2 secretion in colorectal cancer
Presenter: Hideaki Karasawa
Session: Poster Display session 1
Resources:
Abstract
4273 - Paired-related homeobox 1 overexpression promotes invasion and metastasis and is a prognostic factor for worse disease-free survival in patients with lung cancer
Presenter: Jung-jyh Hung
Session: Poster Display session 1
Resources:
Abstract
4241 - LncRNA-GC1 contributes to gastric cancer chemo-resistance through inhibition of miR-551b-3p and the overexpression of dysbindin
Presenter: Xin Guo
Session: Poster Display session 1
Resources:
Abstract
5388 - GLPG 1790, a new selective EPHA2 inhibitor, is active in colorectal cancer cell lines belonging to the CMS4/mesenchymal-like subtype
Presenter: Pietro Paolo Vitiello
Session: Poster Display session 1
Resources:
Abstract
5208 - Characterisation of growth hormone signal transduction in primary melanoma cell lines
Presenter: Karla Sousa
Session: Poster Display session 1
Resources:
Abstract
3156 - LAPTM5 protein can regulate TGF-β mediated MAPK and Smad signaling pathways in ovarian cancer cell
Presenter: Yan Gao
Session: Poster Display session 1
Resources:
Abstract