A newly reported clinical trial used a vaccine that stimulated dendritic cells to treat newly diagnosed advanced melanoma. An immune response was exhibited by six of the seven patients, and three patients had clinically significant changes in the progression of their tumors.
Cancer vaccines prime the immune system to attack cancer cells and decrease cancer progression. Certain types of immune cells produce the cytokine IL-12p70, which has been shown to reduce tumor progression. However, delivering IL-12p70 as part of a cancer vaccine has been limited because of its toxicity in high doses.
Dendritic cells are widely regarded as the most potent antigen-presenting cells for initiating T cell immunity, according to the article, which was published in The Journal of Clinical Investigation (2013; doi: 10.1172/JCI68395). The nature and magnitude of T cell immunity is shaped by immature dendritic cells, indicating the critical role of dendritic cells in the transition from the innate to the adaptive immune system. The research team sought to test the hypothesis that immunization with functionally mature dendritic cells that produced IL-12p70 would correlate with antigen-specific immunity and clinical outcomes in patients with metastatic melanoma.
Beatriz Carreno, PhD, and colleagues at Washington University in St. Louis, Missouri, led the proof-of-concept clinical trial that modified a portion of each patient’s dendritic cells to stimulate increased production of IL-12p70 by their immune system. This method avoided the toxicity seen with previous approaches. The authors explained that, most importantly, levels of IL-12p70 correlated with time to progression.
The authors stated, “These results highlight the critical role of IL-12p70 in developing CD8+ T cell immunity and the potential value of this cytokine as a surrogate for vaccine efficacy and also suggest new strategies to enhance T cell immunity in patients with cancer.”