Mitazalimab

Mitazalimab (ADC-1013; JNJ-64457107) is FcγR-dependent CD40 agonist with tumor-directed activity. Mitazalimab activates antigen-presenting cells, e.g. dendritic cells (DC), to initiate tumor-reactive T cells. Therefore, Mitazalimab induces tumor-specific T cells to infiltrate and kill tumors. Mitazalimab remodels the tumor-infiltrating myeloid microenvironment[1][2].

Research Areas >> Cancer

CD40

Mitazalimab（1 ng/mL-10 μg/mL）可激活人类前列腺肿瘤或卵巢肿瘤样本中的肿瘤相关巨噬细胞 (TAM)[2]。

Mitazalimab（100 μg/小鼠；腹腔注射；单次剂量）激活 naïve hCD40tg 小鼠的脾脏树突细胞和 B 细胞，并在 OVA 再处理条件（200 μg；i.v.；3 次，连续 7 天）下，导致 OVA 特异性 CD8+ T 细胞扩增[1]。 Mitazalimab（100 和 300 μg/小鼠；腹腔注射；接种后第 7、10 和 13 天）诱导携带 MB49（小鼠膀胱肿瘤细胞系）的肿瘤小鼠的血液中促炎细胞因子和趋化因子的释放，并改变肿瘤骨髓细胞组成，减少单核细胞和巨噬细胞，增加粒细胞[1]。 Animal Model: MB49-tumor bearing mice model[1] Dosage: 10, 30, 100 or 300 µg/mouse Administration: Intraperitoneal injection; on day 7, 10 and 13 post-inoculation; sampled at 24 h after final dose Result: Increased the level of IP-10, MIP-1α and TNF-α, but not CXCL1, IFN-γ, IL-6, IL-10, MCP-1 and MIP-2. Resulted in increased frequency of CD44hi CD62L-efector memory CD8+ and CD4+ T cells.

[1]. Deronic A, et al. The human anti-CD40 agonist antibody mitazalimab (ADC-1013; JNJ-64457107) activates antigen-presenting cells, improves expansion of antigen-specific T cells, and enhances anti-tumor efficacy of a model cancer vaccine in vivo. Cancer Immunol Immunother. 2021 Dec;70(12):3629-3642.  

[2]. Smith K E, et al. Mitazalimab, a potent CD40 agonist in combination with chemotherapy redirects and activates tumor infiltrating myeloid cells[J]. Cancer Research, 2022, 82(12_Supplement): 4155-4155.