Triggering anti-GBM immune response with EGFR-mediated photoimmunotherapy

• Published in: BMC medicine Vol. 20; no. 1; pp. 16 - 17
• Main Authors: Mączyńska, Justyna, Raes, Florian, Da Pieve, Chiara, Turnock, Stephen, Boult, Jessica K. R., Hoebart, Julia, Niedbala, Marcin, Robinson, Simon P., Harrington, Kevin J., Kaspera, Wojciech, Kramer-Marek, Gabriela
• Format: Journal Article
• Language: English
• Published: London BioMed Central 21.01.2022; BioMed Central Ltd; BMC
• Subjects: Affibody molecules; Analysis; Animals; Antibodies; Apoptosis; Autoantibodies; Biomedicine; Brain; Brain cancer; Brain research; Brain tumors; Calreticulin; Cancer therapies; Care and treatment; Cell activation; Cell death; Cell Line, Tumor; Cell proliferation; Conjugates; Damage patterns; Dendritic cells; Diagnosis; Epidermal growth factor receptors; ErbB Receptors; Experiments; Flow cytometry; Glioblastoma; Glioblastoma - therapy; Glioblastoma multiforme; Hemorrhage; HMGB1 protein; Hsp70 protein; Humans; Immune response; Immune system; Immunity; Immunogenicity; Immunology; Immunotherapy; In vivo methods and tests; IR700; Irradiation; Kinases; Ligands; Light effects; Light irradiation; Lymphocytes; Lymphocytes T; Magnetic resonance imaging; Medical prognosis; Medical research; Medicine; Medicine & Public Health; Mice; Microenvironments; Mutation; Necrosis; Neoplasm Recurrence, Local; Patient outcomes; Patients; Phenols; Photoimmunotherapy; Photosensitizing Agents; Post-irradiation; Radiation; Radioimmunotherapy; Reactive oxygen species; Research Article; Risk factors; Surgery; Targeted Therapies; Tumor Microenvironment; Tumor suppressor genes; Tumors; Xenograft Model Antitumor Assays; Xenografts; Xenotransplantation; Germany; United Kingdom > UK; United States > US; Photoimmunotherapy; IR700; Affibody molecules; Glioblastoma
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-021-02213-z

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 (Z EGFR:03115 ) was conjugated to IR700. The response to Z EGFR: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 Z EGFR:03115 -IR700 to produce reactive oxygen species upon light irradiation. Z EGFR: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 T 2 *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 Z EGFR: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.