Abstract 3127: Development of three-dimensional cancer cell line spheroid models for the in vitro functional characterization of cytotoxic antibody-drug conjugates

球体 体外 抗体-药物偶联物 细胞毒性T细胞 癌症 药品 结合 细胞培养 癌细胞系 癌症研究 抗体 化学 医学 生物 癌细胞 免疫学 药理学 单克隆抗体 内科学 生物化学 遗传学 数学 数学分析
作者
Jodi Wong,Andrea Hernández Rojas,Allysha Bissessur,Lemlem T. Degefie,Araba Sagoe-Wagner,Samir Das,Vincent Fung,Kevin Yin,Renee Duan,Sam Lawn,Laurence Madera,Catrina Kim,Alexander T.H. Wu,Mark E. Petersen,Raffaele Colombo,Jamie R. Rich,Stuart D. Barnscher
出处
期刊:Cancer Research [American Association for Cancer Research]
卷期号:84 (6_Supplement): 3127-3127
标识
DOI:10.1158/1538-7445.am2024-3127
摘要

Abstract Background: Antibody-drug conjugates (ADCs) are an effective class of cancer therapeutics which have gained prominence for the treatment of several malignancies. A cytotoxic ADC consists of a linker-payload conjugated to a monoclonal antibody, which targets a distinct tumor-associated antigen (TAA) to enable the delivery of the cytotoxic payload to cancer cells. Presently, there is a need for in vitro models that better recapitulate in vivo tumor tissue complexity to aid in the screening and evaluation of ADCs during preclinical development. Hence, efforts have been made to develop in vitro three-dimensional (3D) models with improved translation to in vivo tumor models compared to traditional two-dimensional (2D) cancer cell line monolayer models. We aimed to generate monoculture cancer cell line spheroids in a high-throughput manner. Subsequently, we sought to evaluate the spheroid penetration capability of structurally distinct ADCs and to assess the 3D cytotoxic activity of a variety of microtubule inhibitor (MTI) and topoisomerase 1 inhibitor (TOPO1i)-bearing ADCs targeting multiple TAAs, comparing to activity in 2D models. Methods: Monoculture cancer cell spheroids were generated by seeding cells from a variety of tumor types, using an automated liquid-handling robot, into microtiter plates treated with ultra-low attachment coating, which allows for scaffold-free self-assembly of cancer cells into a 3D arrangement. Following spheroid formation by incubation for 2-3 days under standard culturing conditions, spheroids were treated with ADCs at a range of concentrations for functional evaluation: the spheroid penetration capability of ADCs of different antibody formats was assessed using high-content confocal imaging of spheroids treated with fluorescently labeled antibodies; the cytotoxic activity of ADCs was characterized using an ATP quantification luminescent reagent, live/dead cell fluorescent stains, and confocal imaging. Results: Monoculture spheroids of varying morphologies were successfully and reproducibly generated with a large panel of >50 cancer cell lines derived from >10 tumor types. Antibodies with different formats demonstrated target-mediated binding and a range of spheroid penetration depths. Additionally, MTI and TOPO1i ADCs evaluated in a panel of cancer cell spheroids demonstrated robust 3D cytotoxicity and differentiated activity when compared to the 2D monolayer assay. In a number of cases, the potency trends across multiple ADCs in 3D cytotoxicity assays were more predictive of in vivo efficacy compared to the 2D assay. Taken together, our high-throughput spheroid assays present important and straightforward in vitro tools to aid in the screening and selection of therapeutic cytotoxic ADC candidates for the treatment of solid tumors. Citation Format: Jodi Wong, Andrea Hernández Rojas, Allysha Bissessur, Lemlem T. Degefie, Araba P. Sagoe-Wagner, Samir Das, Vincent Fung, Kevin Yin, Renee Duan, Sam Lawn, Laurence Madera, Catrina Mi Jung Kim, Alex Wu, Mark E. Petersen, Raffaele Colombo, Jamie R. Rich, Stuart D. Barnscher. Development of three-dimensional cancer cell line spheroid models for the in vitro functional characterization of cytotoxic antibody-drug conjugates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3127.

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
绿泡泡发布了新的文献求助10
1秒前
今后应助Transition采纳,获得10
3秒前
Chelry发布了新的文献求助10
3秒前
大大怪发布了新的文献求助10
4秒前
乐乐应助lina采纳,获得10
6秒前
7秒前
7秒前
gz完成签到,获得积分10
10秒前
哲别发布了新的文献求助10
11秒前
SciGPT应助科研通管家采纳,获得10
14秒前
香蕉觅云应助科研通管家采纳,获得10
14秒前
14秒前
充电宝应助科研通管家采纳,获得10
14秒前
李健应助科研通管家采纳,获得10
14秒前
义气严青完成签到,获得积分10
14秒前
15秒前
15秒前
16秒前
20秒前
某某完成签到,获得积分20
22秒前
23秒前
Owen应助shore采纳,获得10
23秒前
小熊完成签到,获得积分10
24秒前
英姑应助丸子_2025000采纳,获得10
25秒前
yydragen应助rita_sun1969采纳,获得30
25秒前
可爱的函函应助大喵采纳,获得10
26秒前
30秒前
包李发布了新的文献求助10
30秒前
31秒前
打打应助自由的读书人采纳,获得10
35秒前
共享精神应助bbh采纳,获得10
36秒前
研友_VZG7GZ应助bbh采纳,获得10
36秒前
小小完成签到,获得积分10
36秒前
大喵发布了新的文献求助10
36秒前
漫奏曲发布了新的文献求助10
37秒前
40秒前
包李完成签到,获得积分10
44秒前
科研小虫完成签到,获得积分10
47秒前
nianxunxi完成签到,获得积分10
48秒前
CipherSage应助一颗椰子糖耶采纳,获得10
48秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
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 3989797
求助须知:如何正确求助?哪些是违规求助? 3531914
关于积分的说明 11255516
捐赠科研通 3270597
什么是DOI,文献DOI怎么找? 1805008
邀请新用户注册赠送积分活动 882181
科研通“疑难数据库(出版商)”最低求助积分说明 809190