Poster Presentation 35th Lorne Cancer Conference 2023

Sustained release of immunotherapy from an intraoperative hydrogel prevents cancer recurrence after surgery   (#315)

Francois Xavier Rwandamuriye 1 , Cameron W Evans 2 , Ben Wylie 1 3 , Breana Vitali 1 , Maren Pfirrmann 1 , Ellise Roper 1 , Marck Norret 4 , Matt S Hepburn 5 6 , Rowan W Sanderson 5 6 , Ken Wyatt 7 8 , Annie L Ryan 1 9 , Terrance G Johns 1 , Marianne B Phillips 1 9 , Rupert Hodder 10 , Brendan F Kennedy 5 6 , Rachael M Zemek 1 3 , K. Swaminathan Iyer 2 , W. Joost Lesterhuis 1 3
  1. Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia
  2. School of Molecular Sciences, The University of Western Australia, Crawley, WA, Australia
  3. Centre for Child Health Research, The University of Western Australia, Crawley, WA, Australia
  4. School of Molecular Sciences, The University of Western Australia, Perth, WA, Australia
  5. BRITElab, Harry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands, WA, Australia
  6. Department of Electrical, Electronic & Computer Engineering, School of Engineering, The University of Western Australia, Crawley, WA, Australia
  7. Perth Veternary Specialists, Osborne Park, WA, Australia
  8. Murdoch Veternary School, Murdoch University, Murdoch, WA, Australia
  9. Department of Clinical Haematology, Tissue & Cellular Therapies, Perth Children's Hospital, Perth, WA, Australia
  10. Department of Surgery, Sir Charles Gairdner Hospital, Nedlands, WA, Australia

Introduction. Surgery is often the first-line treatment option for many solid cancers, usually in combination with chemotherapy and/or radiotherapy. However, relapse of the primary tumour after surgery is common and associated with a poor prognosis. Systemic immunotherapy, especially with checkpoint inhibitors, has provided important improvements in survival in some hard-to-treat cancers such as melanoma and non-small cell lung cancer. However, this often comes with severe side effects due to off-target toxicity. Here, we aimed to develop a hydrogel, which could be easily applied locally during oncological surgery, with the goal to attract and activate immune cells into the tumour resection site to eradicate any remaining tumour cells and prevent post-surgical cancer recurrence.

Methods. We developed a hyaluronic acid-based hydrogel which we optimized to have desired properties for intraoperative application. We assessed the efficacy of the hydrogel-loaded immunotherapy using our established mouse models of partial tumour resection. Next, we characterised the underlying immunological mechanism using cytokine blocking studies, flow cytometry, and RNA sequencing. Finally, we assessed the safety and feasibility of the hydrogel delivery platform in a veterinary canine clinical trial following the surgical removal of canine sarcoma.

Results. The hydrogel could be feasibly applied in the wound bed after cancer surgery. The immunotherapy from the hydrogel, placed in the tumour resection site, prevented tumour recurrence in multiple mouse models. Mechanistically, the immunotherapy induced a transient IFNα response that reshaped the tumour microenvironment (TME) by attracting inflammatory immune cells and depleting T regs from the TME. In addition, RNAseq data show that a pre-existing gene expression signature predicts a response to the immunotherapy-loaded hydrogel. Finally, the hydrogel delivery platform was safe for use in canine cancer patients and easy to use for the surgeon, while the immunotherapy induced a measurable systemic immune response.

Conclusions. The surgically optimized hydrogel provides a safe and effective drug delivery approach to prevent relapse of solid tumours following surgery and can be translated in a real-world oncological setting.