Kirsten Johnson, MD

Keratinocyte carcinomas (KCs) are the most common type of cancer. Though surgical excision is generally curative, there are growing populations of patients with higher associated morbidity and mortality. Current immunotherapies are expensive, frequently intolerable due to side effects, and often limited in their extent or response duration. Effective non-surgical therapeutic options with minimal side effects are needed to reduce or eliminate tumor burden. Adoptive transfer of healthy ex vivo expanded allogeneic natural killer (NK cells) is becoming increasingly utilized as adjunctive treatment for hematologic and solid tumor malignancies as they directly recognize and kill tumor cells, and are well-tolerated. We recently generated a modified version of these that are resistant to TGFß, a potent immunosuppressive cytokine within the tumor microenvironment (TME) of KCs. Our preliminary data demonstrate TGFß-resistant (TGFßi) expanded NK cells acquire a skin resident transcriptional phenotype. Administration of ex vivo-expanded TGFßi NK cells offers the potential to provide adequate numbers of activated, cytotoxic NK cells that persist in the cutaneous tumor, and can overcome the immunosuppressive TME. We are performing 1) a first-in-human, exploratory trial comparing direct intra-tumoral injection of NK vs TGFßi NK cells into KCs and 2) KC xenograft mouse studies to delineate TGFßi NK cell homing to skin tumors. We expect to demonstrate direct skin homing and persistence of injected NK cells within KCs, resulting in reduced tumor volume and a more cytotoxic TME.

Research interests

• Autoimmune Diseases
• Carcinoma Squamous Cell
• Cell and Tissue Based Therapy
• Graft vs Host Disease
• Immunity Innate
• Immunotherapy
• Killer Cells Natural
• Melanoma
• Molecular Biology
• Single Cell Analysis
• Skin Neoplasms
• Translational Research Biomedical