Bempegaldesleukin and Adoptive Cell Transfer Therapy: Preclinical Melanoma Model
Posted: Wednesday, March 11, 2020
Adoptive cell transfer (ACT) therapy has been an effective measure to treat advanced melanoma and other advanced cancers. One drawback to ACT is that it requires high doses of interleukin-2 (IL-2) to proliferate the immune cells, and high doses of IL-2 have been associated with significant morbidity. A preclinical study published in Nature Communications explored the use of ACT without the negative effects of IL-2. Giulia Parisi, PhD, and colleagues at the UCLA Jonsson Comprehensive Cancer Center tested the drug bempegaldesleukin (also known as NKTR-214) concomitantly with ACT in a melanoma mouse model.
Bempegaldesleukin is an IL-2 receptor agonist that has been designated with Breakthrough Therapy status by the U.S. Food and Drug Administration. The resulting drug has a much lower toxicity than IL-2, as it is not broken down as quickly and thus does not require as high of a dose. Mice were treated with activated T lymphocytes followed by either IL-2 or bempegaldesleukin. The activated T cells expressed firefly luciferase, allowing them to be tracked in vivo.
T cells in mice treated with bempegaldesleukin had higher splenic proliferation as well as tumor mobilization and persistence than did mice treated with IL-2 or the vehicle alone. Furthermore, mice treated with bempegaldesleukin showed a decreased tumor volume and a slowed rate of tumor growth.
“Polyfunctionality,” the ability of T cells to secrete multiple types of cytokines, resulting in longer lasting antitumor response, was also evaluated. The T cells of bempegaldesleukin-treated mice had higher polyfunctionality than those treated with IL-2. Finally, researchers examined the blood samples of patients treated with bempegaldesleukin in a phase I clinical trial and found increased polyfunctionality compared with pretreatment blood samples.
The researchers suggest, “NKTR-214 may have the potential to improve the antitumor activity of ACT in humans through increased in vivo expansion and polyfunctionality of the adoptively transferred T cells.”
Disclosure: For full disclosures of the study authors, visit nature.com.