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
Current View