Fractionated Photoimmunotherapy Stimulates an Anti-Tumour Immune Response: An Integrated Mathematical and In Vitro Study

Authors

Mohammad U Zahid
Matthew Waguespack
Rebecca C Harman
Eric M Kercher
Shubhankar Nath
Tayyaba Hasan
Imran Rizvi
Bryan Q Spring
Heiko Enderling

Publication Date

11-1-2024

Journal

British Journal of Cancer

DOI

10.1038/s41416-024-02844-y

PMID

39261715

PMCID

PMC11473784

PubMedCentral® Posted Date

9-11-2024

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Humans, Immunotherapy, Female, Photochemotherapy, Carcinoma, Ovarian Epithelial, Ovarian Neoplasms, Cell Line, Tumor, T-Lymphocytes, Models, Theoretical, ErbB Receptors, Ovarian cancer, Computational science, Nonlinear dynamics

Published Open-Access

yes

Recommended Citation

Zahid, Mohammad U; Waguespack, Matthew; Harman, Rebecca C; et al., "Fractionated Photoimmunotherapy Stimulates an Anti-Tumour Immune Response: An Integrated Mathematical and In Vitro Study" (2024). Faculty, Staff and Student Publications. 3060.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/3060