Carlumab is a humanized, high-affinity monoclonal antibody that targets CCL2[1-2]. Carlumab exerts its effects by specifically binding to and neutralizing CCL2, thereby inhibiting the recruitment and migration of monocytes/macrophages to the tumor microenvironment and reducing angiogenesis. Carlumab has been investigated in research related to solid tumors such as prostate cancer, ovarian cancer, and glioblastoma, as well as idiopathic pulmonary fibrosis[3-4].
In vitro, human peritoneal mesothelial cells were pretreated with Carlumab (30μg/mL) for 30 minutes, followed by stimulation for 24 hours with a medium containing 0.1% SHS (containing chlorhexidine) and 1μg/mL LPS. Carlumab significantly attenuated the migration of THP-1-derived macrophages towards the injured site in the co-culture system[5]. Endometrial cancer cells were treated with Carlumab (5μg/mL) for 24 hours. This treatment was able to neutralize tumor cell-secreted CCL2, significantly inhibiting the migration of THP-1-derived macrophages towards the tumor cells[6].
In vivo, Carlumab (20mg/kg) was administered via intraperitoneal injection to BALB/c nude mice bearing KLE cell xenograft tumors for 29 days. Carlumab treatment effectively reduced tumor volume, decreased serum CCL2 levels, and reduced the infiltration of CD163+ and CD115+ M2-type macrophages within the tumor tissue[6].
References:
[1] Brana I, Calles A, LoRusso PM, et al. Carlumab, an anti-C-C chemokine ligand 2 monoclonal antibody, in combination with four chemotherapy regimens for the treatment of patients with solid tumors: an open-label, multicenter phase 1b study. Target Oncol. 2015 Mar;10(1):111-23.
[2] Raghu G, Martinez FJ, Brown KK, et al. CC-chemokine ligand 2 inhibition in idiopathic pulmonary fibrosis: a phase 2 trial of carlumab. Eur Respir J. 2015 Dec;46(6):1740-50.
[3] Fetterly GJ, Aras U, Meholick PD, et al. Utilizing pharmacokinetics/pharmacodynamics modeling to simultaneously examine free CCL2, total CCL2 and carlumab (CNTO 888) concentration time data. J Clin Pharmacol. 2013 Oct;53(10):1020-7.
[4] Wang C, Wang L, Li Q, et al. Computational Drug Discovery in Ankylosing Spondylitis-Induced Osteoporosis Based on Data Mining and Bioinformatics Analysis. World Neurosurg. 2023 Jun;174:e8-e16.
[5] Sun J, Sun Y, Guo D, et al. Targeting STING to disrupt macrophage-mediated adhesion in encapsulating peritoneal sclerosis. Commun Biol. 2025 Aug 23;8(1):1266.
[6] Ma J, Mao X, Ren Y, et al. Antagonism of estrogen-related receptor-α inhibits mitochondrial oxidative phosphorylation and reduces M2 macrophage infiltration in endometrial cancer. J Immunother Cancer. 2025 Sep 29;13(9):e012521.
Carlumab是一种人源化、高亲和力的抗CCL2[1-2]。Carlumab通过特异性结合并中和CCL2，从而抑制单核细胞/巨噬细胞向肿瘤微环境的募集和迁移，并减少血管生成。Carlumab可用于前列腺癌、卵巢癌、胶质母细胞瘤等实体瘤以及特发性肺纤维化的相关研究[3-4]。
在体外，Carlumab（30μg/mL）处理人腹膜间皮细胞30分钟，随后以含有0.1% SHS（含氯己定）和1μg/mL LPS的培养基刺激24小时。Carlumab可显著抑制共培养系统中THP-1源性巨噬细胞向损伤部位的迁移[5]。Carlumab（5μg/mL）处理子宫内膜癌细胞24小时。Carlumab能够中和肿瘤细胞分泌的CCL2，从而显著抑制共培养系统中THP-1源性巨噬细胞向肿瘤细胞的迁移[6]。
在体内，Carlumab（20mg/kg）腹腔注射于携带KLE细胞异种移植瘤的BALB/c裸鼠。Carlumab能够有效减少肿瘤体积、降低血清CCL2水平，并减少肿瘤组织中的CD163+和CD115+ M2型巨噬细胞浸润[6]。