While melanoma represents only about 1 percent of skin cancers, it is responsible for the majority of skin cancer fatalities. The American Cancer Society (ACS) reported that in 2023, close to 100,000 new melanoma cases would be diagnosed, with close to 8,000 deaths.
We have been studying novel approaches to treating melanoma, in the hopes of developing a significant new therapy that would have significant impact on morbidity and mortality due to this disease.
Interleukin-24 (IL-24) is a cytokine (normally produced by activated monocytes, macrophages & T-helper cells) with cytotoxic and anti-angiogenic activity preferentially towards cancer cells. Thus, we hypothesized it may be feasible use HSC gene transfer to target platelet synthesis, storage and secretion of IL-24 to inhibit tumor growth. To pursue this hypothesis, we have undertaken research to determine if platelets can be genetically modified to deliver anti-oncogenic agents to tumors. Our goal is to develop methods for therapy for cancer by targeting gene products to platelets. As a model, are investigating the ITGA2B gene promoter with respect to its ability to drive megakaryocyte-specific expression of human interleukin-24 as a potential genetic therapy for IL-24 platelets to treat melanoma.
In a previously published study in mice, we determined that physiological agonists of platelet activation induced secretion of IL-24 from genetically modified platelets, thus indicating feasibility for platelets to serve as vehicles to deliver anti-oncogenic agents to tumors. In our study, melanoma challenge in mice treated with genetically modified platelets containing IL-24 can synthesize and store an anti-oncogenic agent, resulting in 50% reduction in melanoma tumor size in mice after 30 days.
These results suggest that targeting anti-oncogenic agents to platelets may be a feasible strategy for direct inhibition of solid tumors in humans. We are pursuing efforts to substantiate these findings.