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.

Mitazalimab (1 ng/mL-10 μg/mL) activates tumor associated macrophages (TAMs) in prostate tumor or ovarian tumor samples from human[2].

Mitazalimab (100 μg/mouse; i.p.; single dose) activates splenic DC and B cells in Naïve hCD40tg mice, and also results expansion of OVA-specifc CD8+ T cells in OVA-rechallenged (200 μg; i.v.; 3 times for 7 days between) mice[1].Mitazalimab (100 and 300 μg/mouse, i.p.; on day 7, 10 and 13 post-inoculation) induces the release of proinfammatory cytokines and chemokines in the blood in MB49 (mouse bladder tumor cell line) bearing mice, and alters the composition of tumor myeloid cells, such that reduces monocytes and macrophages in favor of granulocytic cell[1].

References:
[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.

Mitazalimab (ADC-1013; JNJ-64457107) 是 FcγR 依赖性 CD40 激动剂，具有肿瘤导向活性。Mitazalimab 激活抗原呈递细胞，例如 树突状细胞 (DC)，以启动肿瘤反应性 T 细胞。因此，Mitazalimab 诱导肿瘤特异性 T 细胞浸润并杀死肿瘤。Mitazalimab 可重塑肿瘤浸润性骨髓微环境。

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]。