O09 - Allogeneic NK Cells and Palliative Radiotherapy in the Treatment of Canine Cancer

Abstract: Background

Natural killer (NK) cells are a promising cellular therapy to treat cancer partly because allogeneic sources can be used for off-the-shelf treatment without the risk of graft-versus-host disease. We evaluated the combination of palliative radiotherapy (RT) and allogeneic NK cell transfer in a first-in-dog feasibility trial to speed translation of novel NK modalities in both dogs and people.

Hypothesis/Objectives

Our objective was to establish feasibility and describe preliminary data for safety and outcomes in dogs with unresectable oral melanoma treated with allogeneic NK cells following palliative RT.

Animals

Five dogs with naturally occurring melanoma were enrolled in this IACUC-approved pilot trial. Allogeneic NK cells were expanded from blood obtained from five healthy beagles.

Methods

Patients underwent weekly RTx4 followed by infusion of intravenous allogeneic NK cells (7.5 x 10^6 cells/kg). Peripheral blood was obtained for biochemical and immune monitoring at baseline and day one, seven, and fourteen days post-treatment.

Results

Adverse events related to NK infusion were classified as grade 1 or 2 and included emesis, fever, lymphopenia, metabolic acidosis, and hypoglycemia. Lymphocyte counts decreased one day post NK infusion but increased and peaked on day seven post-infusion. Median survival time was 145 days with maximum and minimum survival times of 445 days and 48 days, respectively.

Conclusions and clinical importance

Allogeneic NK cell infusions appear well tolerated when administered to dogs with melanoma. This proof-of-concept trial provides preliminary data validating the canine model for investigating allogeneic adoptive NK cell transfer alone or in combination with other immunotherapies.