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Tumor organoids targeted by receptor-engineered immune cells: A promising approach for advancing cancer immunotherapy
Qunfang Zhang1, Huazhen Liu1, Xiaoli Zhang2
1Immunology Program, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.
Abstract:
Patient-derived tumor organoids, often referred to as tumor organoids, serve as in vitro tumor models for tumor-related research, such as living biobanks, identification of biomarkers, drug screening and personalized precision medicine. Despite great success of chimeric antigen receptor (CAR)-engineered T cell therapy of B cell malignancies, the efficacy of receptor-engineered immune cell therapy of solid tumors remains suboptimal due to the molecular heterogeneity and immunosuppressive tumor microenvironment. Moreover, direct and extensive clinical studies are limited because of the toxicity of drugs or adoptively transferred immune cells. Thus, more alternative studies using better in vitro models, such as organoids, are needed to identify the target molecules or biomarkers in tumor cells. Tumor organoids have emerged as a suitable in vitro model for evaluating therapeutic efficacy and toxicity of receptor-engineered immune cells (EICs), because 3D structure and genetic characteristics of tumor organoids mimic the solid tumor microenvironment. In this review, we have summarized the recent advances in the application of tumor organoids for innovating and analyzing immunotherapy of cancers using EICs. We have also highlighted their limitations and pinpointed the potential future research direction in order to better evaluate and improve EIC therapy of cancer.
Insights
Patient-derived tumor organoids offer a promising in vitro model for cancer research, aiding in biomarker discovery and personalized medicine. These models are crucial for advancing engineered immune cell therapy against solid tumors.
Area of Science:
- Oncology
- Immunotherapy
- Biotechnology
Background:
- Chimeric antigen receptor (CAR)-engineered T cell therapy shows success in B cell malignancies.
- Engineered immune cell therapy for solid tumors faces challenges due to tumor heterogeneity and immunosuppressive microenvironments.
- Clinical studies of engineered immune cells are limited by toxicity concerns.
Purpose of the Study:
- To review advances in using tumor organoids for cancer immunotherapy research.
- To highlight the utility of tumor organoids in evaluating engineered immune cells (EICs).
- To identify limitations and future directions for EIC therapy using organoid models.
Main Methods:
- Review of recent scientific literature on tumor organoids and engineered immune cells.
- Analysis of the application of tumor organoids in cancer immunotherapy.
- Discussion of the advantages of organoids in mimicking solid tumor microenvironments.
Main Results:
- Tumor organoids serve as effective in vitro models for cancer research, including biomarker identification and drug screening.
- Organoids accurately mimic the 3D structure and genetic characteristics of solid tumors, making them suitable for evaluating EIC efficacy and toxicity.
- Recent advances show the potential of tumor organoids in innovating and analyzing cancer immunotherapy.
Conclusions:
- Tumor organoids are valuable tools for advancing engineered immune cell therapy for solid tumors.
- Further research using organoids is needed to overcome limitations and improve EIC therapy.
- Organoid models facilitate the identification of target molecules and biomarkers for better cancer treatment strategies.
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