# Limited Clinical Efficacy with Potential Adverse Events in a Pilot Study of Autologous Adoptive Cell Therapy in Canine Oral Malignant Melanoma

## TL;DR

A pilot study on a cell therapy for canine oral melanoma found limited effectiveness and potential side effects, suggesting the need for protocol improvements.

## Contribution

This is the first study to explore adoptive cell therapy in canine oral malignant melanoma, highlighting its safety profile and limited clinical efficacy.

## Key findings

- The treatment was well tolerated in 7 out of 10 dogs, but 3 experienced suspected anaphylaxis.
- The median progression-free interval was 49 days, with dogs having progressive disease during treatment showing shorter survival.
- Most patients were in later clinical stages with macroscopic disease, which may have impacted treatment efficacy.

## Abstract

The pilot study explored a type of adoptive cell therapy in canine oral malignant melanoma, by collecting peripheral blood mononuclear cells from tumor-bearing dogs, expanding the cells to a predominantly non-B non-T population in vitro, and re-infusing the cells into dogs. Ten dogs were enrolled. The treatment was well tolerated in seven dogs, while the other three had suspected treatment-related anaphylaxis. The treatment efficacy was limited to a 49-day median progression-free interval, and dogs with progressive disease during treatment had shorter survival. Most of the recruited patients were in a later clinical stage and had macroscopic disease, which might affect the treatment efficacy. Further exploration of this kind of cell therapy in an adjuvant setting could be considered with adequate protocol modification and standardization.

Adoptive cell therapy (ACT) has been studied in several human and canine cancers with some promising clinical outcomes but not in canine oral malignant melanoma (OMM). Our manuscript aimed to explore one kind of ACT, the ex vivo-expanded autologous immune cell infusion in canine OMM, as this tumor remains a treatment dilemma. The study recruited dogs with histopathological diagnoses of oral malignant melanoma, generated their peripheral blood mononuclear cells, expanded them into predominantly non-B non-T cells via stimulations of IL-15, IL-2, and IL-21, and then re-infused the cells into tumor-bearing dogs. Ten dogs were enrolled; three dogs did not report any adverse events; three had a mildly altered appetite; one had a mildly increased liver index, while the other three developed suspected anaphylaxis at different levels. The median progression-free interval was 49 days. Dogs with progressive disease during treatment had a shorter survival. This pilot study indicates limited efficacy with potential adverse events of this ACT. Most recruited patients were in a later stage and had macroscopic disease, which might affect the treatment efficacy. Further exploration of this cell therapy in an adjuvant setting, with adequate protocol modification and standardization, could still be considered.