Triggering anti-GBM immune response with EGFR-mediated photoimmunotherapy.
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Authors
Mączyńska, J
Raes, F
Da Pieve, C
Turnock, S
Boult, JKR
Hoebart, J
Niedbala, M
Robinson, SP
Harrington, KJ
Kaspera, W
Kramer-Marek, G
Raes, F
Da Pieve, C
Turnock, S
Boult, JKR
Hoebart, J
Niedbala, M
Robinson, SP
Harrington, KJ
Kaspera, W
Kramer-Marek, G
Document Type
Journal Article
Date
2022-01-21
Date Accepted
2021-12-09
Abstract
BACKGROUND: Surgical resection followed by chemo-radiation postpones glioblastoma (GBM) progression and extends patient survival, but these tumours eventually recur. Multimodal treatment plans combining intraoperative techniques that maximise tumour excision with therapies aiming to remodel the immunologically cold GBM microenvironment could improve patients' outcomes. Herein, we report that targeted photoimmunotherapy (PIT) not only helps to define tumour location and margins but additionally promotes activation of anti-GBM T cell response. METHODS: EGFR-specific affibody molecule (ZEGFR:03115) was conjugated to IR700. The response to ZEGFR:03115-IR700-PIT was investigated in vitro and in vivo in GBM cell lines and xenograft model. To determine the tumour-specific immune response post-PIT, a syngeneic GBM model was used. RESULTS: In vitro findings confirmed the ability of ZEGFR:03115-IR700 to produce reactive oxygen species upon light irradiation. ZEGFR:03115-IR700-PIT promoted immunogenic cell death that triggered the release of damage-associated molecular patterns (DAMPs) (calreticulin, ATP, HSP70/90, and HMGB1) into the medium, leading to dendritic cell maturation. In vivo, therapeutic response to light-activated conjugate was observed in brain tumours as early as 1 h post-irradiation. Staining of the brain sections showed reduced cell proliferation, tumour necrosis, and microhaemorrhage within PIT-treated tumours that corroborated MRI T2*w acquisitions. Additionally, enhanced immunological response post-PIT resulted in the attraction and activation of T cells in mice bearing murine GBM brain tumours. CONCLUSIONS: Our data underline the potential of ZEGFR:03115-IR700 to accurately visualise EGFR-positive brain tumours and to destroy tumour cells post-conjugate irradiation turning an immunosuppressive tumour environment into an immune-vulnerable one.
Citation
ANNALS OF ONCOLOGY, 2019, 30 pp. ? - ? (1)
DOI
Source Title
Publisher
BMC
ISSN
0923-7534
eISSN
1569-8041
1569-8041
1569-8041
Research Team
Preclinical Molecular Imaging
Pre-Clinical MRI
Targeted Therapy
Pre-Clinical MRI
Targeted Therapy