TY - JOUR
T1 - Persistence of adoptively transferred T cells with a kinetically engineered IL-2 receptor agonist
AU - Parisi, Giulia
AU - Saco, Justin D.
AU - Salazar, Felix B.
AU - Tsoi, Jennifer
AU - Krystofinski, Paige
AU - Puig-Saus, Cristina
AU - Zhang, Ruixue
AU - Zhou, Jing
AU - Cheung-Lau, Gardenia C.
AU - Garcia, Alejandro J.
AU - Grasso, Catherine S.
AU - Tavaré, Richard
AU - Hu-Lieskovan, Siwen
AU - Mackay, Sean
AU - Zalevsky, Jonathan
AU - Bernatchez, Chantale
AU - Diab, Adi
AU - Wu, Anna M.
AU - Comin-Anduix, Begoña
AU - Charych, Deborah
AU - Ribas, Antoni
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-019-12901-3
DO - 10.1038/s41467-019-12901-3
M3 - Article
C2 - 32005809
AN - SCOPUS:85078833535
SN - 2041-1723
VL - 11
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 660
ER -