Investigators are experimenting with how to deliver a new drug, interleukin-15, which enhances the beneficial effects of NK cells for cancer patients
Cancer immunotherapy exploits different techniques for arming the patient’s immune system for fighting cancer. New ideas are continuously being explored. Here, we look at a first-in-human study for interleukin-15 (IL-15) as another example of exploratory cancer immunotherapy research.
Interleukins include several chemical-signaling molecules that are released by leukocytes (blood cells) when prompted by cues in their environment. A burst of interleukins serves to communicate to cells in the immune system that have receptors for that particular interleukin.
The binding of IL-15 to its receptor activates an "immune-enhancing" signaling cascade in natural killer cells (NK cells) and subsets of T cells. On the basis of promising data from animal model studies and bench assays, investigators proceeded with this clinical trial.
To conduct the first-in-human study, IL-15 was produced using genetically engineered bacteria. The purified protein was tested in rhesus macaques (monkeys) with 12 daily injections to assess for toxicity before human use.
The objectives were to determine the safety, adverse event profile, dose-limiting toxicity (DLT), and maximum-tolerated dose (MTD) of IL-15 administered for 12 consecutive days in metastatic cancer patients who had malignant melanoma or renal cell cancer.
Blood samples were collected at defined times and analyzed for NK cells at short intervals as well as weekly out to 6 weeks. At 48 hours after dosing, NK cells had become proliferative. There was a significant increase in NK cells out to 6 weeks; the fold-increase was dependent on the IL-15 dose.
While the effect of IL-15 on NK cells was promising, it was garnered from this study that bolus (one-time) injections spiked the blood IL-15 concentration to levels that resulted in toxicities. The investigators are exploring different dosing regimens for their next study, such as slow-delivery over longer periods in order to limit/reduce toxicity effects while still being effective on NK cells.
HemaCare provides NK cells to support research that can lead to clinical discoveries.
1. Conlon KC, et al. Redistribution, Hyperproliferation, Activation of Natural Killer Cells and CD8 T Cells, and Cytokine Production During First-in-Human Clinical Trial of Recombinant Human Interleukin-15 in Patients With Cancer. J Clin Oncol. 2015 Jan 1;33(1):74-82.