Tumour-derived dendritic cell vaccination as a novel therapy to prevent metastasis and cancer relapse

Project Details

Description

Metastasis, the process of cancer cells disseminating out of a primary tumour to seed tumour development at secondary sites, is the leading cause of cancer-related death. While cancer treatments have greatly improved the last decades, successful treatment of metastatic disease remains a daunting task. Due to the unique potential of immunotherapy to generate long term antitumour memory, treatments targeting metastasis are closer now than ever before. Owing to the unique functions dendritic cells (DCs) perform by bridging the innate and the adaptive immune systems, our lab previously showed that prophylactic vaccination of naïve mice using tumour-derived DCs could protect vaccinated mice from tumour challenge.

In order to evaluate any potential therapy aiming to reduce metastasis incidence, we first set out to develop a model of metastasis that mimicked natural metastasis formation. Previous experiments involving surgical resection of primary tumours from mice yielded inconsistent and highly variable metastatic events. Therefore, we generated a cell line better adapted to lung metastasis by multiple in vivo passages that selected metastatic cancer cells from the lungs of tumour-bearing mice. Surgical resection of tumours formed after metastatic cancer cell implantation resulted in rapid and consistent lung metastasis incidence. Conveniently the surgically resected tumour also provides us with an ideal reservoir for obtaining tumour-derived DCs that can be used to vaccinate recovering mice. Therefore, in the last stage of my PhD project, I would like to 1) evaluate the phenotype of immune cells within lungs are undergoing metastasis development, 2) evaluate the ability of tumour-derived DC vaccination to inhibit natural lung metastasis formation, and 3) identify novel targets that can slow the natural development of lung metastasis.

Overall, this study aims to make use of a brand-new metastasis model to evaluate potential and identify novel therapies specifically targeting metastasis formation. The knowledge generated from this project can be applied immediately in the clinical to improve patient outcome.
AcronymANI297
StatusActive
Effective start/end date1/01/2231/12/22

Flemish discipline codes

  • Other medical and health sciences not elsewhere classified

Keywords

  • Tumour
  • dendritic cell
  • Metastasis
  • Cancer relapse