Agonistic CD40 Antibodies in Cancer Treatment.
Agonistic CD40 Antibodies in Cancer Treatment.
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DOI：
10.3390/cancers13061302
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发表时间：
2021-03-15
期刊：
影响因子：
5.2
通讯作者：
Kluger HM
中科院分区：
文献类型：
--
作者：
Djureinovic D;Wang M;Kluger HM
CD 40是一种共刺激分子，是激活抗原呈递细胞和其他先天性免疫细胞的关键。它在抗肿瘤免疫中起着重要作用，CD 40激动剂已被证明可以在临床前和临床环境中消除肿瘤，单独使用或与其他治疗方式联合使用。在这里，我们评估了CD 40的表达和与其他免疫介质在各种肿瘤类型的协会和审查的潜力CD 40激动剂用于癌症治疗，鉴于增强先天免疫和适应性免疫之间的相互作用的承诺。CD 40在多种抗原呈递细胞上表达。CD 40的刺激通过上调其他共刺激分子、增加抗原呈递、树突状细胞成熟（许可）和活化CD 8 + T细胞而导致炎症。在这里，我们分析了黑色素瘤，肾细胞癌和胰腺癌中癌症基因组图谱的基因表达数据，发现了CD 40与参与抗原呈递和T细胞功能的几个基因之间的相关性，支持进一步探索CD 40激动剂治疗癌症。激动剂CD 40抗体在几种肿瘤模型中诱导了抗肿瘤作用，当与其他治疗（免疫检查点抑制、化疗和集落刺激因子1受体抑制）联合使用时，该作用更为明显。在临床前模型中肿瘤生长的减少和重新编程肿瘤微环境的能力为目前正在早期临床试验中评估的激动性CD 40抗体（APX 005 M、ChiLob 7/4、ADC-1013、SEA-CD 40、selicrelumab和CDX-1140）的临床开发奠定了基础。在这篇文章中，我们专注于CD 40的表达和免疫在癌症中，激动剂人CD 40抗体，及其临床前和临床开发。由于CD 40及其配体对树突状细胞和巨噬细胞以及下游B和T细胞活化的广泛促炎作用，该途径的激动剂可增强其他全身治疗的抗肿瘤活性。
CD40 is a costimulatory molecule that is key for the activation of antigen-presenting cells and other innate immune cells. It plays an important role in anti-tumor immunity, and agonists of CD40 have been shown to eliminate tumors in both pre-clinical and clinical settings, alone and in combination with other treatment modalities. Here we assess the expression of CD40 and associations with other mediators of immunity in a variety of tumor types and review the potential of CD40 agonists for cancer treatment, given the promise of enhancing the interplay between innate and adaptive immunity. CD40 is expressed on a variety of antigen-presenting cells. Stimulation of CD40 results in inflammation by upregulation of other costimulatory molecules, increased antigen presentation, maturation (licensing) of dendritic cells, and activation of CD8+ T cells. Here we analyzed gene expression data from The Cancer Genome Atlas in melanoma, renal cell carcinoma, and pancreatic adenocarcinoma and found correlations between CD40 and several genes involved in antigen presentation and T cell function, supporting further exploration of CD40 agonists to treat cancer. Agonist CD40 antibodies have induced anti-tumor effects in several tumor models and the effect has been more pronounced when used in combination with other treatments (immune checkpoint inhibition, chemotherapy, and colony-stimulating factor 1 receptor inhibition). The reduction in tumor growth and ability to reprogram the tumor microenvironment in preclinical models lays the foundation for clinical development of agonistic CD40 antibodies (APX005M, ChiLob7/4, ADC-1013, SEA-CD40, selicrelumab, and CDX-1140) that are currently being evaluated in early phase clinical trials. In this article, we focus on CD40 expression and immunity in cancer, agonistic human CD40 antibodies, and their pre-clinical and clinical development. With the broad pro-inflammatory effects of CD40 and its ligand on dendritic cells and macrophages, and downstream B and T cell activation, agonists of this pathway may enhance the anti-tumor activity of other systemic therapies.
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影响因子：
15.3
作者：
Bonifaz, L;Bonnyay, D;Mahnke, K;Rivera, M;Nussenzweig, MC;Steinman, RM
通讯作者：
Steinman, RM
影响因子：
82.9
作者：
Fairfax BP;Taylor CA;Watson RA;Nassiri I;Danielli S;Fang H;Mahé EA;Cooper R;Woodcock V;Traill Z;Al-Mossawi MH;Knight JC;Klenerman P;Payne M;Middleton MR
通讯作者：
Middleton MR
DOI：
10.4049/jimmunol.1600146
发表时间：
2016-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Byrne KT;Leisenring NH;Bajor DL;Vonderheide RH
通讯作者：
Vonderheide RH
影响因子：
11.5
作者：
Fransen, Marieke F.;Sluijter, Marjolein;Melief, Cornelis J. M.
通讯作者：
Melief, Cornelis J. M.
影响因子：
10.1
作者：
Bajor, David L.;Xu, Xiaowei;Vonderheide, Robert H.
通讯作者：
Vonderheide, Robert H.