Skip to main content
eScholarship
Open Access Publications from the University of California

UCLA

UCLA Previously Published Works bannerUCLA

Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist.

  • Author(s): 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
  • et al.
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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View