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Triggering anti-GBM immune response with EGFR-mediated photoimmunotherapy. | LitMetric

AI Article Synopsis

  • Scientists are studying a new treatment for a type of brain tumor called glioblastoma (GBM) that helps patients live longer but often comes back after treatment.
  • They combined a special light therapy with a molecule called Z-IR700, which targets the tumor and helps activate the immune system against it.
  • The results showed that this treatment not only helps doctors see the tumor better but also destroys tumor cells and makes the body’s immune system stronger against the cancer.

Article 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 (Z) was conjugated to IR700. The response to Z-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-IR700 to produce reactive oxygen species upon light irradiation. Z-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*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-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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8780306PMC
http://dx.doi.org/10.1186/s12916-021-02213-zDOI Listing

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