Abstract 4199: rhIL-7-hyFc (efineptakinalpha; NT-I7) enhances the anti-tumor response when combined with hIL-2/TCB2c complex

• Published in: Cancer research (Chicago, Ill.) Ill.), 2022-06, Vol.82 (12_Supplement), p.4199-4199
• Main Authors: Baek, Seungtae, Im, Sun-Kyoung, Lee, Minji, Ji, Mankyu, Kim, Miyoung, Kim, Daeun, Lee, Jun Young, Choi, Donghoon
• Format: Article
• Language: English
• ISSN: 1538-7445; 1538-7445
• DOI: 10.1158/1538-7445.AM2022-4199

rhIL-7-hyFc (efineptakin-alfa; NT-I7) is a potent T cell amplifier, with a homodimeric interleukin-7 (IL-7) fused to the hybridizing IgD/IgG4 immunoglobulin domain. Previous work has shown that in mice, NT-I7 dramatically increases tumor-infiltrating CD8+ T cells while reducing the frequency of PD-1+ CD8+ T cells in the tumor. There is also significant expansion of Central Memory (CM)-phenotype CD8+ T cells (CD62L+CD44+) in the tumor and tumor draining lymph node. Here, we investigated the anti-tumor effect of NT-I7 in combination with a T cell activator, SLC-3010 (hIL-2/TCB2c complex), in MC38 tumor-bearing mice. Because TCB2 is an antibody specific for IL-2 that blocks interaction of IL-2 and IL-2Rα (CD25), SLC-3010 can selectively activate T cells while disfavoring Treg activation. Mice were administered a single dose of NT-I7 or SLC-3010 via intramuscular or intravenous injection, respectively. The combination of NT-I7 with SLC-3010 enhanced the anti-tumor response with increased number and frequency of CD8+ T cells as well as granzyme B expression in the tumor. The number of CD8+ T cells peaked at day 4 and day 7 by SLC-3010 and NT-I7, respectively. The number of Tregs in the tumor was slightly increased by NT-I7 and SLC-3010, but it was not statistically significant. Interestingly, NT-I7, but not SLC-3010, increased the frequency of PD-1+TCF-1+TOX- stem-like CD8+ T cells in the draining lymph node. Meanwhile, SLC-3010 significantly increased the number of PD-1+ CD8+ T cells in the tumor. Our data suggests that NT-I7 can be applied in combination with other immunotherapies such as IL-2 to enhance the anti-tumor response. Citation Format: Seungtae Baek, Sun-Kyoung Im, Minji Lee, Mankyu Ji, Miyoung Kim, Daeun Kim, Jun Young Lee, Donghoon Choi. rhIL-7-hyFc (efineptakinalpha; NT-I7) enhances the anti-tumor response when combined with hIL-2/TCB2c complex [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4199.