Patient‐derived organoids of bladder cancer recapitulate antigen expression profiles and serve as a personal evaluation model for CAR‐T cells in vitro
Open accessAbstract
Objectives: Recent advances in patient‐derived cancer organoids have opened a new avenue for personalised medicine. We aimed to establish an in vitro technological platform to evaluate chimeric antigen receptor (CAR)‐T cell‐mediated cytotoxicity against bladder cancer. Methods: Patient‐derived bladder cancer organoids (BCOs) were derived using classic medium containing R‐spondin 1 and noggin. The features of BCOs were characterised via H&E, whole‐exome sequencing and immunofluorescence of specific markers. Surface antigen expression profiles of the recently identified CAR‐recognisable targets were determined with a panel of antibodies via immunohistochemistry. A co‐cultivation system consisting of BCOs and engineered T cells targeting a specific antigen was utilised to test its efficacy to model immunotherapy by cytotoxic assays and ELISA. Results: Bladder cancer organoid lines of basal and luminal subtypes were established. The histopathological morphology, genomic alteration, and specific marker expression profiles showed that the BCO lines retained the characteristics of the original tumors. Among all tested CAR‐recognisable antigens in other solid tumors, MUC1 was simultaneously expressed in organoids and parental tumor tissues. Given the surface antigen profiles, second‐generation CAR‐T cells targeting MUC1 were prepared for modelling in vitro immunotherapy responses in BCOs. Specific immune cytotoxicity occurred only in the MUC1+ organoids but not in the MUC1‐ organoids or control CAR‐T cells. Conclusion: Patient‐derived BCOs recapitulate the heterogeneity and key features of parental cancer tissues, and these BCOs could be useful for preclinical testing of CAR‐T cells in vitro.
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Deep targeted sequencing of 500 cancer-associated genes showed truncal mutations were retained while subclonal mutations were gained or lost, with mutational changes at each passage.
“Using deep targeted sequencing of 500 cancer-associated genes, truncal mutations were shown to be retained while subclonal ones are gained or lost, with mutational changes at each passage127.”
From Organoids (2022) · cites this paper as [127]
The Results section, “Bladder cancer organoid lines retain the mutational spectrum of the parental tumors” (page unavailable), reports that mutations in the original tumors were retained in derived organoids. The Methods section, “Whole-exome sequencing and analysis” (page unavailable), specifies whole-exome sequencing, not targeted sequencing of 500 genes. The paper does not report truncal-versus-subclonal mutation changes or changes at each passage. (LLM, conf=0.88)
Experimental — accuracy not yet measuredLee and colleagues showed that organoid lines derived from bladder tumors of lumenal origin, when transplanted in mice, gave rise to tumors with the same lumenal phenotype.
“Lee and colleagues showed how organoid lines derived from bladder tumors of lumenal origin transplanted in mice gave rise to tumors with the same lumenal phenotype127.”
From Organoids (2022) · cites this paper as [127]
The Results section (page unavailable) reports that organoids derived from bladder tumors retained their parental tumors’ luminal or basal subtype. It does not report transplanting those organoids into mice or assessing the phenotype of tumors grown in mice. The cited paper is also by Yu and colleagues, not Lee and colleagues. (LLM, conf=0.87)
Experimental — accuracy not yet measuredSeveral studies have found concordance between tumor organoids and parent tissue in mutations and copy number variations.
“Several studies have shown concordance of organoids and parent tissue in terms of mutations and copy number variations (CNV)15,127.”
From Organoids (2022) · cites this paper as [127]
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- Authors
- Yu, L., Li, Z., Mei, H., Li, W., Chen, D., Liu, L., Zhang, Z., Sun, Y., Song, F., Chen, W., & Huang, W.
- Affiliations
- Shenzhen University (CN)
- Corresponding author
- Chen, Wei
- Huang, Weiren
- Venue
- Clinical & Translational Immunology
- Publisher
- Wiley
- Published
- 2021-01
- Volume
- 10
- Issue
- 2
- Pages
- e1248-e1248
- ISSN
- 2050-0068 (ISSN-L)
- PMC
- PMC7847802
- OpenAlex
- W3128579898
- Cited by
- 113
- References
- 45
- Citations by year
- 2026: 24 · 2025: 29 · 2024: 24 · 2023: 18 · 2022: 15 · 2021: 2
- FWCI
- 5.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Clinical & Translational Immunology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (31670757, 81772737)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Health Sciences › Medicine › Surgery › Bladder and Urothelial Cancer Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- bladder cancer, patient-derived organoids, chimeric antigen receptor T cells, MUC1, surface antigen expression, RSPO1, noggin, personalized medicine
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