Research project (completed)

Local targeted immunotherapy for treatment of squamous cell carcinomas

Systemic treatments can give serious side effects, including the risk of autoimmune activation. The aim of the project is to develop a new treatment strategy for patients with skin cancer by turning current systemically administered immunotherapy into use in an effective local treatment strategy.

In my PhD project, I have investigated how the use of laser can be incorporated into immunotherapeutic treatment of skin cancer. I have been testing topical delivery of monoclonal antibodies using ablative fractional laser, needle-free injection and conventional needle injection. My studies have shown that laser can deliver anti-PD-1 antibodies both in vitro and in vivo. When visualizing anti-PD-1 absorbed in the skin, we can see a horizontal homogeneous distribution that reaches the middle skin layer.

In continuation of that, I have investigated the effect of laser treatment on tumors in an in vivo squamous cell model, as well as in combination with immunotherapeutic substances with a focus on PD-1 inhibitors. The study showed that combined treatment with AFL and anti-PD-1 therapy resulted in significantly more tumors disappearing compared to the use of either anti-PD-1 therapy or laser alone. To investigate topical delivery, I used various techniques such as ELISA, fluorescence microscopy and laser ablation-inductively coupled plasma-mass spectometry (LA-ICP-MS).

 

Researcher

Master of Science (MSc) in Human Biology, PhD student Rikke Louise Christensen

Project supervisors

Merete Hædersdal

Uffe Høgh Olesen

Søren Husted

Silje Haukali Omland

Project period

Year: 2019-2023

Project collaborators

Department of Plant and Environmental Sciences, Faculty of Science, University of Copenhagen

Financing

  • Bispebjerg and Frederiksberg Hospital 
  • Greater Copenhagen Health Science Partners (SCIN CAG)
  • Fabrikant Vilhelm Pedersens og Hustrus Mindelegat
  • Danish Research Center for Skin Cancer

Selected publications

Christensen RL, Omland SH, Persson DP, Husted S, Haedersdal M, Olesen UH. Topical Delivery of Nivolumab, a Therapeutic Antibody, by Fractional Laser and Pneumatic Injection. Lasers Surg Med. 2021 Jan;53(1):154-161.

Christensen RL, Hendel KK, Persson DP, Husted S, Olesen UH, Haedersdal M. Topical delivery of PD-1 inhibitors with laser-assisted passive diffusion and active intradermal injection: Investigation of cutaneous pharmacokinetics and biodistribution patterns. Lasers Surg Med. 2022 Jan. 54(1):170-181.