Preclinical testing of chimeric antigen receptor T cells in neuroblastoma mouse models
Nan Li1, Rosa Nguyen2, Carol J Thiele2
1Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
The translation of chimeric antigen receptor (CAR) T cell therapy for pediatric solid tumors is limited by the lack of preclinical models that fully recapitulate solid tumor biology. We describe steps to implement neuroblastoma metastatic and orthotopic mouse models. We delineate an analysis pipeline to quantify the efficacy and determine the immunological characteristics of both CAR T and tumor cells in these models. Both mouse models can be applied to evaluate other experimental therapies for neuroblastoma. For complete details on the use and execution of this protocol, please refer to Li et al. (2021).
Insights
Developing new preclinical models for chimeric antigen receptor (CAR) T-cell therapy in pediatric solid tumors is crucial. This study details neuroblastoma mouse models and an analysis pipeline to assess CAR T-cell efficacy and tumor immunology.
Area of Science:
- Oncology
- Immunology
- Preclinical Research
Background:
- Chimeric antigen receptor (CAR) T-cell therapy shows promise for pediatric cancers.
- Translating CAR T-cell therapy to pediatric solid tumors is hindered by inadequate preclinical models.
- Neuroblastoma is a challenging pediatric solid tumor for current therapies.
Purpose of the Study:
- To establish and validate neuroblastoma mouse models for preclinical CAR T-cell therapy research.
- To develop an analysis pipeline for evaluating CAR T-cell efficacy and tumor immunology in these models.
- To provide a resource for testing novel therapeutic strategies against neuroblastoma.
Main Methods:
- Implementation of metastatic and orthotopic neuroblastoma mouse models.
- Development of an analysis pipeline to quantify CAR T-cell efficacy.
- Assessment of immunological characteristics of CAR T-cells and tumor cells within the models.
Main Results:
- Established functional neuroblastoma mouse models suitable for CAR T-cell therapy evaluation.
- Delineated a comprehensive analysis pipeline for assessing therapeutic efficacy and immune responses.
- Demonstrated the utility of these models for evaluating experimental therapies.
Conclusions:
- The developed neuroblastoma mouse models and analysis pipeline are valuable tools for advancing pediatric solid tumor research.
- These models facilitate the preclinical evaluation of CAR T-cell therapy and other experimental treatments for neuroblastoma.
- This work addresses a critical need for robust preclinical models in pediatric oncology.
