Human Microtumors Generated in 3D: Novel Tools for Integrated In Situ Studies of Cancer Immunotherapies
Lothar Hambach1,2, Andreas Buser3,4, Marcel Vermeij5
1Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leident, The Netherlands. hambach.lothar@mh-hannover.de.
Abstract:
Cellular immunotherapy targeting human tumor antigens is a promising strategy to treat solid tumors. Yet clinical results of cellular immunotherapy are disappointing. Moreover, the currently available in vitro human tumor models are not designed to study the optimization of T-cell therapies of solid tumors. Here, we describe a novel assay for multiparametric in situ analysis of therapeutic effects on individual human three-dimensional (3D) tumors. In this assay, tumors of several millimeter diameter are generated from human cancer cell lines of different tumor entities in a collagen type I microenvironment. A newly developed approach for efficient morphological analysis reveals that these in vitro tumors resemble many characteristics of the corresponding clinical cancers such as histological features, immunohistochemical staining patterns, distinct tumor growth compartments and heterogeneous protein expression. To assess the response to therapy with tumor antigen specific T-cells, standardized protocols are described to determine T-cell infiltration and tumor destruction by monitoring soluble factors and tumor growth. Human tumors engineered in 3D collagen scaffolds are excellent in vitro surrogates for avascular tumor stages allowing integrated analyses of the antitumor efficacy of cancer specific immunotherapy in situ.
Insights
A new in vitro assay using 3D human tumors in collagen scaffolds enables multiparametric analysis of cellular immunotherapy efficacy. This model improves the study of T-cell therapies for solid tumors.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Cellular immunotherapy shows promise for solid tumors but faces clinical limitations.
- Existing in vitro models inadequately support the study of T-cell therapy optimization for solid tumors.
Purpose of the Study:
- To develop a novel assay for multiparametric in situ analysis of therapeutic effects on individual human three-dimensional (3D) tumors.
- To establish a more accurate in vitro model for evaluating T-cell therapies against solid tumors.
Main Methods:
- Generation of millimeter-sized human tumors from cancer cell lines within a collagen type I microenvironment.
- Development of an efficient morphological analysis approach to characterize in vitro tumors.
- Standardized protocols for assessing T-cell infiltration, tumor destruction, soluble factors, and tumor growth.
Main Results:
- The 3D in vitro tumors exhibit characteristics similar to clinical cancers, including histological features and heterogeneous protein expression.
- The assay allows for in situ monitoring of T-cell infiltration and antitumor effects.
- The model effectively mimics avascular tumor stages for immunotherapy assessment.
Conclusions:
- Human tumors engineered in 3D collagen scaffolds serve as effective in vitro surrogates for avascular tumor stages.
- This novel assay facilitates integrated analyses of antitumor efficacy for cancer-specific immunotherapy in situ.
- The developed model aids in optimizing T-cell therapies for solid tumors.
