Combo against melanoma
Researchers from the Johnsson Cancer Center at the University of California, Los Angeles, have shown that the use of the experimental immunotherapy drug NKTR-214, also known as bempegaldesleukin, in combination with an infusion of antitumor immune cells can cause a powerful immune response that will help in the fight against progressive melanoma.
NKTR-214 is an inactive form of interleukin-2. The protein in its composition is conjugated with several chains of polyethylene glycol, which prevent it from binding to interleukin-2 receptors. However, when exposed to certain physiological conditions, polyethylene glycol chains are sequentially released, allowing the cytokine to connect with specific receptors and initiate signal transmission.
When tested on mouse models of melanoma, this approach increased the number of antitumor immune cells, the animals lived longer and functioned better than during standard therapy.
Changes in the average tumor volume over time in three groups of mice: adoptive cell therapy (gray graph), adoptive cell therapy plus interleukin-2 (purple graph), adoptive cell therapy plus NKTR-214 (green graph). Time is marked on the X scale, and the average volume of the tumor is marked on the Y scale. Source: article in Nature Communications.
Adoptive cell therapy is a type of immunotherapy designed to treat people with cancer in the late stages. The approach involves taking immune cells from a patient and modifying them in the laboratory to attack certain antigens located on the surface of tumor cells. One of the problems of adoptive therapy is that the patient needs to be injected with the signaling molecule interleukin-2 to stimulate the growth and development of the immune cells introduced after the change. But interleukin-2 can also activate cells that suppress immune responses and, because it is highly toxic, cause serious side effects.
The researchers focused on finding ways to obtain a large number of immune cells without the risk of negative side effects, including by combining adoptive cell therapy with other treatments.
The researchers tested the drug NKTR-214 in combination with adoptive cell therapy on mice. Using bioluminescent imaging, they tracked the movement of T cells in mice receiving combination therapy. The group observed an increase in T cells in the spleen. From there, the T cells migrated to the tumor, where they continued to function and had a lasting effect. The accumulation of T cells in tumors was more significant with NKTR-214 therapy than in mice treated with interleukin-2.
Thus, NKTR-214 in combination with adoptive cell therapy may be an effective way to treat more people with advanced solid tumors.
New research in this area is needed.
Article by G.Parisi et al. Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist is published in the journal Nature Communications.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on UCLA Newsroom: Researchers identify possible new combination treatment for advanced melanoma.