PhD defence by Sophie Bjørn Jensen

On Monday 26 June 2023, Sophie Bjørn Jensen will defend her PhD thesis "Development of immune polarizing intratumoral drug delivery technologies".

Time: 13:00

Place: Building 341, auditorium 22

Principal supervisor: Professor Thomas Lars Andresen

Co-supervisor: Senior Researcher Anders Elias Hansen

Associate Professor Jonas Rosager Henriksen

Assessment committee:
Senior Researcher Jannik Larsen, DTU Health Tech

Associate Professor Daniel H. Madsen, National Center for Cancer Immune Therapy

Associate Professor Lambros Tselikas, InSerm/Gustave Rouussy

Chairperson:
Associate Professor Paul Kempen, DTU Health Tech

Abstract:
Cancer is a leading cause of death worldwide, and people all over the world are affected by this disease. Surgery, chemotherapy, and radiation therapy have been the standard of care for many years, but in recent times, immunotherapy has emerged as a promising strategy for anticancer treatment. Compared to traditional cancer treatments, which are directed against the cancerous cells, cancer immunotherapy is directed toward cells of the immune system. Accordingly, immunotherapy aims to stimulate the immune cells to indirectly attack and kill the cancerous cells. Unfortunately, systemic administration of immunostimulatory agents, that bridge the innate and adaptive immune systems, is often associated with immune-related adverse events at sub-therapeutic dose levels, limiting their clinical use. Intratumoral injection offers a strategy to circumvent this, however, injection of free drugs is often hampered by rapid drug clearance from the tumor and reduced efficacy. A drug delivery platform providing sustained release of immunostimulatory agents directly in the tumor tissue has the potential to overcome these challenges.
The overall aim of the work presented in this thesis was to provide a preclinical evaluation of intratumoral treatment with immunotherapy delivered in the novel CarboCell drug delivery platform. The CarboCell delivery platform has been developed within the group and provides sustained release of immunostimulatory agents selectively within the tumor microenvironment. In the studies presented in this thesis, the CarboCell platform was formulated to release a Tolllike receptor 7/8 agonist alone or in combination with a transforming growth factor-β inhibitor. Intratumoral administration of CarboCell immunotherapy led to impressive therapeutic efficacy across several murine cancer models without compromising tolerability. CarboCell treatment, further, resulted in the activation of the innate and adaptive immune systems and in induction of a systemic response.
Collectively, this thesis offers a preclinical evaluation of intratumoral sustained drug delivery using the CarboCell platform, highlighting the potential of the CarboCell technology as a part of future anticancer treatment strategies.