IL-7 After Sipuleucel-T for Advanced Prostate Cancer
Posted: Friday, December 18, 2020
For patients with advanced metastatic prostate cancer, the sipuleucel-T vaccination improves overall survival, although the benefits are often short-term. Caroline Duault, PharmD, PhD, of Stanford University, California, and colleagues suggested that interleukin 7 (IL-7) may benefit patients after sipuleucel-T vaccination by promoting T-cell activation and improving the duration of efficacy. The results of this phase II clinical trial were presented at the 2020 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 263) and published in the Journal for ImmunoTherapy of Cancer.
The trial tested the therapeutic potential of human recombinant glycosylated IL-7 after sipuleucel-T therapy on asymptomatic patients with advanced prostate cancer. Using a variation of mass cytometry, cytometry by time-of-flight analysis, the researchers tested peripheral blood mononuclear cells at baseline (week 1) and 6 weeks after the start of IL-7 therapy.
Among patients who received IL-7 therapy, the researchers observed an increase in the number of circulating T lymphocytes, especially CD8 T cells. The number of CD4 T cells did not seem to increase, although the cells demonstrated greater functionality; upon stimulation by PMA (phorbol myristate acetate)-ionomycin, the study authors observed increased expression of IL-2, TNFα, and IL-6. The IL-7 therapy also seemed to have a positive effect on cytotoxic subsets. The research group observed increased expression of interferon gamma in CD8 T cells, TNFα in natural killer cells, and IL-2 in γδ T cells. Although there was a reduction in the number of circulating monocytes, these cells showed high TNFα expression.
“Altogether, our data revealed multiple effects of IL-7 in these patients, highlighting a complex set of in vivo mechanisms,” the researchers concluded. “In the future, knowledge of these effects may help in choosing the best agents to use in combination with IL-7 [or] the best patients to benefit from IL-7 as part of their therapeutic approach.”
Disclosure: For study authors’ disclosures, visit jitc.bmj.com.