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Establishing Intracranial Brain Tumor Xenografts With Subsequent Analysis of Tumor Growth and Response to Therapy using Bioluminescence Imaging
Published on: July 13, 2010
Compartment-Specific Bioluminescence Imaging platform for the high-throughput evaluation of antitumor immune function
Douglas W McMillin1, Jake Delmore, Joseph M Negri
1Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Blood
|February 1, 2012
Summary
A new imaging technique (CS-BLI) enables high-throughput screening of drugs and cells to quantify innate antitumor activity. This method reveals how various agents and stromal cells modulate immune responses against tumors, identifying potential new cancer therapies.
Area of Science:
- Immunology
- Pharmacology
- Biotechnology
Background:
- Conventional assays for immune effector cell antitumor activity lack high-throughput capabilities.
- Evaluating immunomodulatory agents and their effects on antitumor immunity requires efficient methods.
Purpose of the Study:
- To adapt Compartment-Specific Bioluminescence Imaging (CS-BLI) for high-throughput quantification of innate antitumor activity.
- To investigate the modulatory effects of pharmacologic agents and bone marrow stromal cells on antitumor immunity.
- To establish a framework for identifying and prioritizing novel immunomodulatory compounds for clinical development.
Main Methods:
- Adaptation of Compartment-Specific Bioluminescence Imaging (CS-BLI) for high-throughput screening.
- Evaluation of pharmacologic agents (lenalidomide, pomalidomide, bortezomib, dexamethasone) and autologous BM stromal cells.
- Quantification of innate antitumor activity and immune effector cell responses.
Main Results:
- CS-BLI enabled high-throughput identification of agents that enhance or inhibit innate antitumor cytotoxicity.
- Demonstrated heterogeneous immunomodulatory pharmacologic responses across different tumor cell types.
- Identified compounds with differential effects, stimulating activity against some tumors while suppressing it against others.
Conclusions:
- CS-BLI provides a rapid, simplified, and specific method for evaluating multiple conditions affecting antitumor immunity.
- The study highlights the heterogeneity of drug responses in immunomodulation.
- This framework aids in discovering novel immunomodulatory agents and prioritizing compounds for clinical trials based on their impact on antitumor immunity.
