학술논문
Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist.
Document Type
article
Author
Parisi, Giulia; Saco, Justin D; Salazar, Felix B; Tsoi, Jennifer; Krystofinski, Paige; Puig-Saus, Cristina; Zhang, Ruixue; Zhou, Jing; Cheung-Lau, Gardenia C; Garcia, Alejandro J; Grasso, Catherine S; Tavaré, Richard; Hu-Lieskovan, Siwen; Mackay, Sean; Zalevsky, Jonathan; Bernatchez, Chantale; Diab, Adi; Wu, Anna M; Comin-Anduix, Begoña; Charych, Deborah; Ribas, Antoni
Source
Nature communications. 11(1)
Subject
Language
Abstract
Interleukin-2 (IL-2) is a component of most protocols of adoptive cell transfer (ACT) therapy for cancer, but is limited by short exposure and high toxicities. NKTR-214 is a kinetically-engineered IL-2 receptor βγ (IL-2Rβγ)-biased agonist consisting of IL-2 conjugated to multiple releasable polyethylene glycol chains resulting in sustained signaling through IL-2Rβγ. We report that ACT supported by NKTR-214 increases the proliferation, homing and persistence of anti-tumor T cells compared to ACT with IL-2, resulting in superior antitumor activity in a B16-F10 murine melanoma model. The use of NKTR-214 increases the number of polyfunctional T cells in murine spleens and tumors compared to IL-2, and enhances the polyfunctionality of T and NK cells in the peripheral blood of patients receiving NKTR-214 in a phase 1 trial. In conclusion, 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.