Cancer treatment with recombinant interleukin-15 and cyclophosphamide

Abstract

Interleukin-15 (IL-15) is a pleiotropic cytokine that plays a pivotal role in innate and adaptive immunity. Therefore, it is a promising therapeutic agent for cancer treatment. Despite growing interest in the use of IL-15 as an immunotherapeutic agent, there have been very few reports on its immunological and clinical effects in canine cancers. In this study, we generated recombinant canine IL-15 (rcIL-15) and evaluated its clinical and immunomodulatory effects in combination with metronomic cyclophosphamide in 15 canines with various tumor types. The treatment outcomes were assessed in a prospective clinical trial. Low-dose cyclophosphamide (12.5 mg/m, PO, SID) was continuously administered for 8 weeks. Starting on day 14, after administering cyclophosphamide, rcIL-15 (20 μg/kg daily) was injected intravenously for 8 days. The disease control rate for combination therapy was 66.6 %, with the most notable partial response accounting for 33.3 % of hematological malignancies. The adverse events were minimal and primarily of grade 1 severity. Moreover, rcIL-15 administration led to significant elevations in anticancer lymphocyte subsets, such as natural killer and cytotoxic T cells, along with increased Ki-67 expression, indicating cellular proliferation. These changes were correlated with improved clinical outcomes. Our findings underscore the therapeutic potential and safety of combining rcIL-15 and metronomic cyclophosphamide for the treatment of various canine cancers.