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Open Access 01-01-2017 | Original Article

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

Authors: Sylvia Herter, Laura Morra, Ramona Schlenker, Jitka Sulcova, Linda Fahrni, Inja Waldhauer, Steffi Lehmann, Timo Reisländer, Irina Agarkova, Jens M. Kelm, Christian Klein, Pablo Umana, Marina Bacac

Published in: Cancer Immunology, Immunotherapy | Issue 1/2017

Abstract

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.

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Title: A novel three-dimensional heterotypic spheroid model for the assessment of the activity of cancer immunotherapy agents
Authors: Sylvia Herter
Laura Morra
Ramona Schlenker
Jitka Sulcova
Linda Fahrni
Inja Waldhauer
Steffi Lehmann
Timo Reisländer
Irina Agarkova
Jens M. Kelm
Christian Klein
Pablo Umana
Marina Bacac
Publication date: 01-01-2017
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 1/2017
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-016-1927-1

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