Avelumab (Anti-Human PD-L1, Human Antibody) is an intravenously (i.v.) administered fully human IgG1 monoclonal antibody (mAb)[1]. Avelumab can inhibit the interaction between PD-L1 and PD-1 and mediate antibody-dependent cell-mediated cytotoxicity (ADCC) through retention of its native FcR, leading to the reinvigoration of effector T cells [2]. Avelumab has been widely used to inhibit tumor progression in different tumor models and to develop novel combination therapies to enhance synergistic anti-tumor effects[3].
In vitro, Avelumab treatment at 20μg/ml for 7 days increased IFN-γ levels and decreased IL-5 concentrations in peripheral blood mononuclear cells (PBMC)[4]. Incubation with 2μg/ml Avelumab for 30min increased the sensitivity of IFN-γ-treated UM-Chor1 cells to natural killer (NK) lysis[5]. Treatment with Avelumab at 2μg/ml for 24h promoted NK cell disinhibition and enhanced the cytotoxicity against HPV-positive cervical cancer cells[6].
In vivo, Avelumab treatment, at a dose of 400µg/100µl intraperitoneally every three days for 9 days, significantly inhibited tumor growth in C57BL/6 mice bearing MB49 subcutaneous tumors and substantially improved 60-day survival[7]. Intraperitoneal injection of Avelumab at a dose of 400µg every 2 days for one week significantly delayed MC38 tumor growth in C57BL/6 mice and increased CD8+ T cell frequency in mouse spleen[8].
References:
[1] Kim E S. Avelumab: first global approval[J]. Drugs, 2017, 77(8): 929-937.
[2] Collins J M, Gulley J L. Product review: avelumab, an anti-PD-L1 antibody[J]. Human vaccines & immunotherapeutics, 2019, 15(4): 891-908.
[3] Bourhis J, Stein A, de Boer J P, et al. Avelumab and cetuximab as a therapeutic combination: An overview of scientific rationale and current clinical trials in cancer[J]. Cancer treatment reviews, 2021, 97: 102172.
[4] Grenga I, Donahue R N, Lepone L M, et al. A fully human IgG1 anti‐PD‐L1 MAb in an in vitro assay enhances antigen‐specific T‐cell responses[J]. Clinical & translational immunology, 2016, 5(5): e83.
[5] Fujii R, Friedman E R, Richards J, et al. Enhanced killing of chordoma cells by antibody-dependent cell-mediated cytotoxicity employing the novel anti-PD-L1 antibody avelumab[J]. Oncotarget, 2016, 7(23): 33498.
[6] Liu H, Zhou S, Liu J, et al. Lirilumab and avelumab enhance anti-HPV+ cervical cancer activity of natural killer cells via Vav1-dependent NF-κB disinhibition[J]. Frontiers in oncology, 2022, 12: 747482.
[7] Vandeveer A J, Fallon J K, Tighe R, et al. Systemic immunotherapy of non-muscle invasive mouse bladder cancer with avelumab, an anti–PD-L1 immune checkpoint inhibitor[J]. Cancer immunology research, 2016, 4(5): 452-462.
[8] Fallon J K, Vandeveer A J, Schlom J, et al. Enhanced antitumor effects by combining an IL-12/anti-DNA fusion protein with avelumab, an anti-PD-L1 antibody[J]. Oncotarget, 2017, 8(13): 20558.
Avelumab (Anti-Human PD-L1, Human Antibody)是一种静脉给药的完全人源化IgG1单克隆抗体[1]。Avelumab能抑制PD-L1与PD-1之间的相互作用，并通过保留天然的FcR介导抗体依赖性细胞介导的细胞毒性（ADCC），从而重新激活效应T细胞[2]。Avelumab已被广泛用于抑制不同肿瘤模型中的肿瘤进展，并开发新型联合疗法以增强协同抗肿瘤效应[3]。
在体外，使用20µg/ml的Avelumab处理7天，提高了外周血单个核细胞（PBMC）中IFN-γ的水平并降低了IL-5的浓度[4]。用2µg/ml的Avelumab孵育30分钟，增加了经IFN-γ处理的UM-Chor1细胞对自然杀伤（NK）细胞裂解的敏感性[5]。使用2µg/ml的Avelumab处理24小时，促进了NK细胞的抑制解除，并增强了NK细胞对HPV阳性宫颈癌细胞的细胞毒性[6]。
在体内，每隔三天腹腔注射Avelumab（剂量为400µg/100µl），持续9天，显著抑制了携带MB49皮下肿瘤的C57BL/6小鼠中的肿瘤生长，并大幅提高了60天存活率[7]。每隔两天腹腔注射Avelumab（剂量为400µg），持续一周，显著延迟了C57BL/6小鼠中MC38肿瘤的生长，并增加了小鼠脾脏中CD8+ T细胞的频率[8]。