- 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
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.