Neuroblastoma and DIPG Organoid Coculture System for Personalized Assessment of Novel Anticancer Immunotherapies.
| Title: | Neuroblastoma and DIPG Organoid Coculture System for Personalized Assessment of Novel Anticancer Immunotherapies. |
|---|---|
| Authors: | M Kholosy W; Princess Máxima Center for Paediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.; Derieppe M; Princess Máxima Center for Paediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.; van den Ham F; Princess Máxima Center for Paediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.; Ober K; Princess Máxima Center for Paediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.; Su Y; Princess Máxima Center for Paediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.; Custers L; Princess Máxima Center for Paediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.; Schild L; Princess Máxima Center for Paediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.; M J van Zogchel L; Princess Máxima Center for Paediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.; M Wellens L; Princess Máxima Center for Paediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.; R Ariese H; Princess Máxima Center for Paediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.; Szanto CL; Princess Máxima Center for Paediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.; Wienke J; Princess Máxima Center for Paediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.; Dierselhuis MP; Princess Máxima Center for Paediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.; van Vuurden D; Princess Máxima Center for Paediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.; Dolman EM; Princess Máxima Center for Paediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands.; Molenaar JJ; Princess Máxima Center for Paediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht, The Netherlands. |
| Source: | Journal of personalized medicine [J Pers Med] 2021 Aug 30; Vol. 11 (9). Date of Electronic Publication: 2021 Aug 30. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: MDPI AG Country of Publication: Switzerland NLM ID: 101602269 Publication Model: Electronic Cited Medium: Print ISSN: 2075-4426 (Print) Linking ISSN: 20754426 NLM ISO Abbreviation: J Pers Med Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI AG, 2011- |
| Abstract: | Cancer immunotherapy has transformed the landscape of adult cancer treatment and holds a great promise to treat paediatric malignancies. However, in vitro test coculture systems to evaluate the efficacy of immunotherapies on representative paediatric tumour models are lacking. Here, we describe a detailed procedure for the establishment of an ex vivo test coculture system of paediatric tumour organoids and immune cells that enables assessment of different immunotherapy approaches in paediatric tumour organoids. We provide a step-by-step protocol for an efficient generation of patient-derived diffuse intrinsic pontine glioma (DIPG) and neuroblastoma organoids stably expressing eGFP-ffLuc transgenes using defined serum-free medium. In contrast to the chromium-release assay, the new platform allows for visualization, monitoring and robust quantification of tumour organoid cell cytotoxicity using a non-radioactive assay in real-time. To evaluate the utility of this system for drug testing in the paediatric immuno-oncology field, we tested our in vitro assay using a clinically used immunotherapy strategy for children with high-risk neuroblastoma, dinutuximab (anti-GD2 monoclonal antibody), on GD2 proficient and deficient patient-derived neuroblastoma organoids. We demonstrated the feasibility and sensitivity of our ex vivo coculture system using human immune cells and paediatric tumour organoids as ex vivo tumour models. Our study provides a novel platform for personalized testing of potential anticancer immunotherapies for aggressive paediatric cancers such as neuroblastoma and DIPG. |
| References: | J Neurosurg Pediatr. 2017 May;19(5):518-530. (PMID: 28291423); Pharmacol Ther. 2017 Oct;178:31-47. (PMID: 28322974); Hum Gene Ther. 2015 Dec;26(12):826-40. (PMID: 26414116); Curr Protoc Immunol. 2018 Feb 21;120:3.11.1-3.11.29. (PMID: 29512145); Commun Biol. 2019 May 9;2:156. (PMID: 31098401); Nat Rev Cancer. 2013 Jun;13(6):397-411. (PMID: 23702928); Trends Immunol. 2020 Aug;41(8):652-664. (PMID: 32654925); Cancer Res. 1984 Dec;44(12 Pt 1):5914-20. (PMID: 6498849); Nat Rev Immunol. 2020 May;20(5):279-293. (PMID: 31853049); J Transl Med. 2014 Oct 04;12:278. (PMID: 25280402); Glycoconj J. 2011 May;28(3-4):137-47. (PMID: 21519903); Nat Med. 2018 Aug;24(8):1204-1215. (PMID: 29967352); Clin Cancer Res. 2020 Jul 1;26(13):3319-3332. (PMID: 32165429); Oncotarget. 2017 Jul 28;8(44):76644-76655. (PMID: 29100338); Nat Commun. 2020 Mar 11;11(1):1310. (PMID: 32161258); BMC Cancer. 2019 Oct 21;19(1):970. (PMID: 31638925); J Virol. 1998 Nov;72(11):8463-71. (PMID: 9765382); Eur J Cancer. 2014 Feb;50(3):628-37. (PMID: 24321263); MethodsX. 2018 Feb 27;5:173-183. (PMID: 30622915); Cancer Res. 1985 Jun;45(6):2642-9. (PMID: 2580625); Cancers (Basel). 2019 Dec 14;11(12):. (PMID: 31847387); PLoS One. 2014 Feb 19;9(2):e89357. (PMID: 24586714); J Cell Biochem. 2005 Sep 1;96(1):1-7. (PMID: 16052484); Annu Rev Biomed Eng. 2002;4:235-60. (PMID: 12117758); J R Soc Interface. 2014 Jul 6;11(96):. (PMID: 24829281); Br J Cancer. 2015 Feb 17;112(4):693-703. (PMID: 25628092); Nat Med. 2017 Apr;23(4):483-492. (PMID: 28263309); PLoS One. 2017 Jan 4;12(1):e0169485. (PMID: 28052119); N Engl J Med. 2010 Sep 30;363(14):1324-34. (PMID: 20879881) |
| Contributed Indexing: | Keywords: cancer immunotherapy; coculture system; diffuse intrinsic pontine glioma (DIPG); neuroblastoma; paediatric cancer organoids |
| Entry Date(s): | Date Created: 20210928 Latest Revision: 20211001 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC8466534 |
| DOI: | 10.3390/jpm11090869 |
| PMID: | 34575646 |
| Database: | MEDLINE |
Journal Article