Fractionated photoimmunotherapy stimulates an anti-tumour immune response: an integrated mathematical and in vitro study

Br J Cancer. 2024 Nov;131(8):1378-1386. doi: 10.1038/s41416-024-02844-y. Epub 2024 Sep 11.

Abstract

Background: Advanced epithelial ovarian cancer (EOC) has high recurrence rates due to disseminated initial disease presentation. Cytotoxic phototherapies, such as photodynamic therapy (PDT) and photoimmunotherapy (PIT, cell-targeted PDT), have the potential to treat disseminated malignancies due to safe intraperitoneal delivery.

Methods: We use in vitro measurements of EOC tumour cell and T cell responses to chemotherapy, PDT, and epidermal growth factor receptor targeted PIT as inputs to a mathematical model of non-linear tumour and immune effector cell interaction. The model outputs were used to calculate how photoimmunotherapy could be utilised for tumour control.

Results: In vitro measurements of PIT dose responses revealed that although low light doses (<10 J/cm2) lead to limited tumour cell killing they also increased proliferation of anti-tumour immune effector cells. Model simulations demonstrated that breaking up a larger light dose into multiple lower dose fractions (vis-à-vis fractionated radiotherapy) could be utilised to effect tumour control via stimulation of an anti-tumour immune response.

Conclusions: There is promise for applying fractionated PIT in the setting of EOC. However, recommending specific fractionated PIT dosimetry and timing will require appropriate model calibration on tumour-immune interaction data in human patients and subsequent validation of model predictions in prospective clinical trials.

MeSH terms

  • Carcinoma, Ovarian Epithelial / immunology
  • Carcinoma, Ovarian Epithelial / radiotherapy
  • Carcinoma, Ovarian Epithelial / therapy
  • Cell Line, Tumor
  • ErbB Receptors / immunology
  • Female
  • Humans
  • Immunotherapy* / methods
  • Models, Theoretical
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / radiotherapy
  • Ovarian Neoplasms / therapy
  • Photochemotherapy* / methods
  • T-Lymphocytes / immunology
  • T-Lymphocytes / radiation effects

Substances

  • ErbB Receptors