IL-7 Therapy Boosts Immune Response in Cancer Patients
July 4, 2008 — Data from a preliminary study suggest that recombinant human interleukin (r-hIL)-7 can enhance and broaden immune responses in patients with impaired immunity due to lymphocyte depletion.
The results of the phase 1 trial, published online June 23 in The Journal of Experimental Medicine, showed that when given to cancer patients, rhIL-7 induced a dramatic polyclonal prolonged expansion of CD4+ and CD8+ T cells, which in turn caused a significant broadening of circulating T cell receptor repertoire diversity. These effects were mediated primarily through an increase in peripheral T cell cycling and augmented cell survival.
Lymphopenia induced by cytotoxic chemotherapy, or pathologies such as HIV infection, can significantly weaken immune function; as a physiologic immuno-enhancer, IL-7 can enhance the restoration of T cells. CD4+ T cell recovery in adults who have experienced severe depletion requires the reemergence of a pool of naive T cells, which generally takes 18 to 24 months and might only occur in people younger than 40 to 45 years. Thus, the authors note, a strategy that can accelerate or promote the recovery of a widely diverse T cell repertoire in older people might be useful for a large number of clinical applications.
“We know that IL-7 can enhance tumor vaccines in animals, so that would be a clear avenue of research,” said lead author Claude Sportès, MD, senior staff clinician at the National Cancer Institute’s Center for Cancer Research, Experimental Transplantation and Immunology Branch, in Bethesda, Maryland. “But it wouldn’t only have to be tumor vaccines. Hopefully we will have a trial underway in the not-too-distant future looking at how it can enhance anti-viral and other immunizations, particularly in the elderly.”
Treatment with IL-7 therapy exerted a marked effect on T cell immune reconstitution during preliminary trials with animal models. It also appeared to augment effector and memory responses to vaccination in mice; in preclinical models, IL-7 therapy was able to augment anti-tumor responses that might improve survival when combined with anti-tumor vaccines.
“In older individuals, therapy with IL-7 could lead to a rejuvenation of the phenotype,” explained Dr. Sportès in an interview. “This in turn can lead to better vaccine responses in general and, in oncology, better tumor vaccine responses.”
The implications for rhIL-7 are potentially vast, and there are many promising therapeutic avenues. “But as often happens in medicine,” he cautioned, “things can be very promising at this stage and then fizzle out.”
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