Clinical toxicity of antibody drug conjugates: a meta-analysis of payloads

医学 毒性 中性粒细胞减少症 白细胞减少症 加药 内科学 贫血 药理学 养生 肿瘤科
作者
Joanna C. Masters,Dana J. Nickens,Dawei Xuan,Ronald Shazer,Michael Amantea
出处
期刊:Investigational New Drugs [Springer Science+Business Media]
卷期号:36 (1): 121-135 被引量:237
标识
DOI:10.1007/s10637-017-0520-6
摘要

Background Antibody drug conjugates (ADCs) utilize a monoclonal antibody to deliver a cytotoxic payload specifically to tumor cells, limiting exposure to healthy tissues. Major clinical toxicities of ADCs include hematologic, hepatic, neurologic, and ophthalmic events, which are often dose-limiting. These events may be off-target effects caused by premature release of payload in circulation. A meta-analysis was performed to summarize key clinical safety data for ADCs by payload, and data permitting, establish a dose-response model for toxicity incidence as a function of payload, dose/regimen, and cancer type. Methods A literature search was performed to identify and extract data from clinical ADC studies. Toxicity incidence and severity were collected by treatment arm for anemia, neutropenia, thrombocytopenia, leukopenia, hepatic toxicity, peripheral neuropathy, and ocular toxicity. Exploratory plots, descriptive summaries, and logistic regression modelling were used to explore Grade ≥ 3 (G3/4) toxicities and assess the impact of covariates, including cancer type and dose/regimen. Results The dataset contained 70 publications; quantitative analysis included 43 studies with G3/4 toxicity information reported for the endpoints above. G3/4 anemia, neutropenia and peripheral neuropathy were consistently reported for MMAE ADCs, thrombocytopenia and hepatic toxicity for DM1, and ocular toxicity for MMAF. Safety profiles of MMAE, DM1, and DM4 ADCs differed between solid and hematologic cancers. Conclusions Published ADC clinical data is limited by non-uniform reporting for toxicity and lack of dosing information, limiting the ability to develop quantitative models relating toxicity to exposure. However, the current analysis suggests that key G3/4 toxicities of ADCs in the clinic are likely off-target and related to payload.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
黄花完成签到 ,获得积分10
1秒前
刘珍荣完成签到,获得积分10
2秒前
2秒前
紫金之巅完成签到 ,获得积分10
2秒前
Gang完成签到,获得积分10
3秒前
4秒前
4秒前
5秒前
CYYDNDB完成签到 ,获得积分10
5秒前
粿粿一定行完成签到 ,获得积分10
6秒前
7秒前
战战完成签到,获得积分10
8秒前
xlk2222完成签到,获得积分10
11秒前
笨笨以莲完成签到,获得积分10
11秒前
YHX完成签到,获得积分10
12秒前
沐沐心完成签到 ,获得积分10
13秒前
13秒前
14秒前
哭泣笑柳发布了新的文献求助10
14秒前
轻松白桃完成签到,获得积分10
14秒前
JasVe完成签到 ,获得积分10
17秒前
wakkkkk完成签到,获得积分10
17秒前
含蓄听南完成签到,获得积分10
17秒前
HH给HH的求助进行了留言
17秒前
芋你呀完成签到,获得积分10
18秒前
西蓝花香菜完成签到 ,获得积分10
18秒前
无花果应助兔子采纳,获得10
18秒前
请勿继续完成签到,获得积分10
20秒前
搞怪的婴完成签到,获得积分10
21秒前
Loooong完成签到,获得积分0
21秒前
23秒前
fuguier完成签到,获得积分10
25秒前
大橙子发布了新的文献求助10
25秒前
王旭完成签到,获得积分10
27秒前
轻松白桃发布了新的文献求助10
27秒前
27秒前
Distance发布了新的文献求助10
28秒前
鲤鱼青雪完成签到,获得积分10
28秒前
耳机单蹦完成签到,获得积分10
29秒前
苻醉山完成签到 ,获得积分0
29秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038184
求助须知:如何正确求助?哪些是违规求助? 3575908
关于积分的说明 11373872
捐赠科研通 3305715
什么是DOI,文献DOI怎么找? 1819255
邀请新用户注册赠送积分活动 892662
科研通“疑难数据库(出版商)”最低求助积分说明 815022