Nanrilkefusp alfa

Nanrilkefusp alfa (SO-C101; SOT101) is fusion protein, is a selective and potent agonist fusion protein of IL-15 and IL-15Rα sushi+ domain. Nanrilkefusp alfa inhibits tumor by inducing proliferation and activation of memory CD8+ T cells, natural killer (NK) cells, γ/δ T cells and NKT cells. Nanrilkefusp alfa exhibits excellent anti-metastatic activity against melanoma and suppresses tumor growth in various mouse tumor models[1][2].

Research Areas >> Cancer

Signaling Pathways >> Immunology/Inflammation >> Interleukin Related

IL-15

IL-15Rα

Nanrilkefusp alfa (0.01-10 nM; 7 d) 能够在体外扩增并激活来源于人 PBMC 细胞的自然杀伤 (NK) 细胞亚型[1]。 Nanrilkefusp alfa (1 nM; 20 h) 能够诱导人 NK 细胞亚型的细胞毒性和肿瘤细胞杀伤活性[1]。 Nanrilkefusp alfa (0.1, 1，和 10 nM; 3 天和 7 天) 诱导 NK 细胞上细胞毒受体 NKp30、DNAM-1 和 NKG2D 的表达[1]。

Nanrilkefusp alfa (2 mg/kg; 皮下注射; 连续 4 天给药, 共 2 周) 降低依赖于自然杀伤细胞 (NK) 和 CD8+ T 细胞的 TC-1 小鼠肿瘤模型的肿瘤发展和生长速度。在该肿瘤模型中，Nanrilkefusp 也能激活自然杀伤细胞和 CD8+ T 细胞中的毒性基因[1]。 Nanrilkefusp alfa (1 mg/kg; 腹腔注射; 连续 4 天, 共 2 周)，与 12.5 mg/kg 抗 PD-1 剂，可降低 TRAMP-C2 小鼠肿瘤模型的肿瘤生长，并扩增了 CD8+ T 细胞和自然杀伤细胞群体，但不会增加调节性 T 细胞 (Treg) 的数目。Nanrilkefusp alfa 也介导了主要依赖于自然杀伤细胞和 CD8+ T 细胞的 TRAMP-C2 肿瘤发展的抑制[1]。 Animal Model: TC-1 mouse tumor model[1] Dosage: 2 mg/kg Administration: Subcutaneous injection; for 4 consecutive days over 2 weeks Result: Decreased the rate of the tumor development. Decreased the tumor growth of established TC-1 tumors in dependence on NK and CD8+ T cells, but not CD4+ T cells. Expanded immune cells in tumor, lymph nodes and spleen and activates NK and CD8+ T cytotoxicity genes in TC-1 tumor mouse model. Animal Model: TRAMP-C2 tumors mouse model[1] Dosage: 1 mg/kg; with or without 12.5 mg/kg anti-PD-1 Administration: Intraperitoneal injection; for 4 consecutive days over 2 weeks Result: Prevented tumor development with anti-PD-1 in the majority of TRAMP-C2 mouse and delays tumor growth after re-challenge.

[1]. Antosova Z, et al. SOT101 induces NK cell cytotoxicity and potentiates antibody-dependent cell cytotoxicity and anti-tumor activity. Front Immunol. 2022 Oct 10;13:989895.  

[2]. Adkins I, et al. SO-C101 displays strong anti-tumor effect in TC-1 and TRAMP-C2 tumor mice and in combination with PD-1 blockade prevents tumor development in a NK and CD8⁺ T cells dependent manner[J]. Cancer Research, 2020, 80(16_Supplement): 6686-6686.