Abstract
Abstract 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 two different T cell suppressor blockades; anti-TIGIT (YH29143) and anti-VEGF (Aflibercept) in MC38 tumor-bearing mice. NT-I7 was administered by intramuscular injection with the first dose of either YH29143 or Aflibercept. YH29143 or Aflibercept was administered every 3 days for 3 total doses, via intraperitoneal or intravenous route, respectively. The combination of NT-I7 with either T cell suppressor blockade enhanced the anti-tumor response. Surprisingly, NT-I7 combined with YH29143 increased the frequency of PD-1+TCF-1+TOX-CD39- stem-like CD8+ T cells in the draining lymph node. The combination also dramatically increased the frequency of CD62L-CD44+ effector memory CD8+ T cells in the tumor. Surprisingly, NT-I7 combined with YH29143 increased the frequency of PD-1+TCF-1+TOX-CD39- stem-like CD8+ T cells in the draining lymph node. In addition, Aflibercept reduced the expression of TOX in PD-1+ CD8+ T cells in the tumor. Our data suggests that NT-I7 can be applied in combination with other immunotherapies such as anti-TIGIT or anti-VEGF to enhance the anti-tumor response. Citation Format: Seungtae Baek, Sun-Kyoung Im, Minji Lee, Mankyu Ji, Miyoung Kim, Kwang-Hoon Lee, Yun Hee Choi, Won Tae Kim, Donghoon Choi. rhIL-7-hyFc (efineptakin alpha; NT-I7) enhances the anti-tumor response when combined with anti-TIGIT or anti-VEGF [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 4172.
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