A novel three-dimensional heterotypic spheroid model for the assessment of the activity of cancer immunotherapy agents

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• 作者：Sylvia Herter ; Laura Morra ; Ramona Schlenker…
• 关键词：Cancer immunotherapy ; 3D model ; Heterotypic spheroid model ; T cell bispecific antibodies ; Interleukin ; 2 immunocytokine fusion ; Tumor–stroma interaction
• 刊名：Cancer Immunology, Immunotherapy
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：66
• 期：1
• 页码：129-140
• 全文大小：1204KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Oncology; Immunology; Cancer Research;
• 出版者：Springer Berlin Heidelberg
• ISSN：1432-0851
• 卷排序：66

文摘

The complexity of the tumor microenvironment is difficult to mimic in vitro, particularly regarding tumor–host interactions. To enable better assessment of cancer immunotherapy agents in vitro, we developed a three-dimensional (3D) heterotypic spheroid model composed of tumor cells, fibroblasts, and immune cells. Drug targeting, efficient stimulation of immune cell infiltration, and specific elimination of tumor or fibroblast spheroid areas were demonstrated following treatment with a novel immunocytokine (interleukin-2 variant; IgG-IL2v) and tumor- or fibroblast-targeted T cell bispecific antibody (TCB). Following treatment with IgG-IL2v, activation of T cells, NK cells, and NKT cells was demonstrated by increased expression of the activation marker CD69 and enhanced cytokine secretion. The combination of TCBs with IgG-IL2v molecules was more effective than monotherapy, as shown by enhanced effects on immune cell infiltration; activation; increased cytokine secretion; and faster, more efficient elimination of targeted cells. This study demonstrates that the 3D heterotypic spheroid model provides a novel and versatile tool for in vitro evaluation of cancer immunotherapy agents and allows for assessment of additional aspects of the activity of cancer immunotherapy agents, including analysis of immune cell infiltration and drug targeting.