Accelerating development of high-risk neuroblastoma patient-derived xenograft models for preclinical testing and personalised therapy.
Journal
British journal of cancer
ISSN: 1532-1827
Titre abrégé: Br J Cancer
Pays: England
ID NLM: 0370635
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
27
06
2019
accepted:
20
09
2019
revised:
18
09
2019
pubmed:
11
1
2020
medline:
21
10
2020
entrez:
11
1
2020
Statut:
ppublish
Résumé
Predictive preclinical models play an important role in the assessment of new treatment strategies and as avatar models for personalised medicine; however, reliable and timely model generation is challenging. We investigated the feasibility of establishing patient-derived xenograft (PDX) models of high-risk neuroblastoma from a range of tumour-bearing patient materials and assessed approaches to improve engraftment efficiency. PDX model development was attempted in NSG mice by using tumour materials from 12 patients, including primary and metastatic solid tumour samples, bone marrow, pleural fluid and residual cells from cytogenetic analysis. Subcutaneous, intramuscular and orthotopic engraftment were directly compared for three patients. PDX models were established for 44% (4/9) of patients at diagnosis and 100% (5/5) at relapse. In one case, attempted engraftment from pleural fluid resulted in an EBV-associated atypical lymphoid proliferation. Xenogeneic graft versus host disease was observed with attempted engraftment from lymph node and bone marrow tumour samples but could be prevented by T-cell depletion. Orthotopic engraftment was more efficient than subcutaneous or intramuscular engraftment. High-risk neuroblastoma PDX models can be reliably established from diverse sample types. Orthotopic implantation allows more rapid model development, increasing the likelihood of developing an avatar model within a clinically useful timeframe.
Sections du résumé
BACKGROUND
Predictive preclinical models play an important role in the assessment of new treatment strategies and as avatar models for personalised medicine; however, reliable and timely model generation is challenging. We investigated the feasibility of establishing patient-derived xenograft (PDX) models of high-risk neuroblastoma from a range of tumour-bearing patient materials and assessed approaches to improve engraftment efficiency.
METHODS
PDX model development was attempted in NSG mice by using tumour materials from 12 patients, including primary and metastatic solid tumour samples, bone marrow, pleural fluid and residual cells from cytogenetic analysis. Subcutaneous, intramuscular and orthotopic engraftment were directly compared for three patients.
RESULTS
PDX models were established for 44% (4/9) of patients at diagnosis and 100% (5/5) at relapse. In one case, attempted engraftment from pleural fluid resulted in an EBV-associated atypical lymphoid proliferation. Xenogeneic graft versus host disease was observed with attempted engraftment from lymph node and bone marrow tumour samples but could be prevented by T-cell depletion. Orthotopic engraftment was more efficient than subcutaneous or intramuscular engraftment.
CONCLUSIONS
High-risk neuroblastoma PDX models can be reliably established from diverse sample types. Orthotopic implantation allows more rapid model development, increasing the likelihood of developing an avatar model within a clinically useful timeframe.
Identifiants
pubmed: 31919402
doi: 10.1038/s41416-019-0682-4
pii: 10.1038/s41416-019-0682-4
pmc: PMC7054410
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
680-691Commentaires et corrections
Type : CommentIn
Références
Kaatsch, P. Epidemiology of childhood cancer. Cancer Treat. Rev. 36, 277–285 (2010).
pubmed: 20231056
Matthay, K. K., Maris, J. M., Schleiermacher, G., Nakagawara, A., Mackall, C. L., Diller, L. et al. Neuroblastoma. Nat. Rev. Dis. Primers 2, 16078 (2016).
pubmed: 27830764
Pinto, N. R., Applebaum, M. A., Volchenboum, S. L., Matthay, K. K., London, W. B., Ambros, P. F. et al. Advances in risk classification and treatment strategies for neuroblastoma. J. Clin. Oncol. 33, 3008–3017 (2015).
pubmed: 26304901
pmcid: 4567703
London, W. B., Bagatell, R., Weigel, B. J., Fox, E., Guo, D., Van Ryn, C. et al. Historical time to disease progression and progression-free survival in patients with recurrent/refractory neuroblastoma treated in the modern era on Children's Oncology Group early-phase trials. Cancer. 123, 4914–4923 (2017).
pubmed: 28885700
pmcid: 5716896
Cohen, L. E., Gordon, J. H., Popovsky, E. Y., Gunawardene, S., Duffey-Lind, E., Lehmann, L. E. et al. Late effects in children treated with intensive multimodal therapy for high-risk neuroblastoma: high incidence of endocrine and growth problems. Bone Marrow Transplant. 49, 502–508 (2014).
pubmed: 24442245
Applebaum, M. A., Henderson, T. O., Lee, S. M., Pinto, N., Volchenboum, S. L. & Cohn, S. L. Second malignancies in patients with neuroblastoma: the effects of risk-based therapy. Pediatr. Blood Cancer 62, 128–133 (2015).
pubmed: 25251613
Fletcher, J. I., Ziegler, D. S., Trahair, T. N., Marshall, G. M., Haber, M. & Norris, M. D. Too many targets, not enough patients: rethinking neuroblastoma clinical trials. Nat. Rev. Cancer 18, 389–400 (2018).
pubmed: 29632319
Kurmasheva, R. T. & Houghton, P. J. Identifying novel therapeutic agents using xenograft models of pediatric cancer. Cancer Chemother. Pharmacol. 78, 221–232 (2016).
pubmed: 27193096
pmcid: 4966996
Zarzosa, P., Navarro, N., Giralt, I., Molist, C., Almazan-Moga, A., Vidal, I. et al. Patient-derived xenografts for childhood solid tumors: a valuable tool to test new drugs and personalize treatments. Clin. Transl. Oncol. 19, 44–50 (2017).
pubmed: 27718156
Byrne, A. T., Alferez, D. G., Amant, F., Annibali, D., Arribas, J., Biankin, A. V. et al. Interrogating open issues in cancer precision medicine with patient-derived xenografts. Nat. Rev. Cancer 17, 254–268 (2017).
pubmed: 28104906
Hidalgo, M., Amant, F., Biankin, A. V., Budinska, E., Byrne, A. T., Caldas, C. et al. Patient-derived xenograft models: an emerging platform for translational cancer research. Cancer Discov. 4, 998–1013 (2014).
pubmed: 25185190
pmcid: 4167608
Daniel, V. C., Marchionni, L., Hierman, J. S., Rhodes, J. T., Devereux, W. L., Rudin, C. M. et al. A primary xenograft model of small-cell lung cancer reveals irreversible changes in gene expression imposed by culture in vitro. Cancer Res. 69, 3364–3373 (2009).
pubmed: 19351829
pmcid: 2821899
Tentler, J. J., Tan, A. C., Weekes, C. D., Jimeno, A., Leong, S., Pitts, T. M. et al. Patient-derived tumour xenografts as models for oncology drug development. Nat. Rev. Clin. Oncol. 9, 338–350 (2012).
pubmed: 22508028
pmcid: 3928688
Blattmann, C., Thiemann, M., Stenzinger, A., Roth, E. K., Dittmar, A., Witt, H. et al. Establishment of a patient-derived orthotopic osteosarcoma mouse model. J. Transl. Med. 13, 136 (2015).
pubmed: 25926029
pmcid: 4428092
Hidalgo, M., Bruckheimer, E., Rajeshkumar, N. V., Garrido-Laguna, I., De Oliveira, E., Rubio-Viqueira, B. et al. A pilot clinical study of treatment guided by personalized tumorgrafts in patients with advanced cancer. Mol. Cancer Ther. 10, 1311–1316 (2011).
pubmed: 21673092
pmcid: 4629061
Kim, M. P., Evans, D. B., Wang, H., Abbruzzese, J. L., Fleming, J. B. & Gallick, G. E. Generation of orthotopic and heterotopic human pancreatic cancer xenografts in immunodeficient mice. Nat. Protoc. 4, 1670–1680 (2009).
pubmed: 19876027
pmcid: 4203372
Monsma, D. J., Monks, N. R., Cherba, D. M., Dylewski, D., Eugster, E., Jahn, H. et al. Genomic characterization of explant tumorgraft models derived from fresh patient tumor tissue. J. Transl. Med. 10, 125 (2012).
pubmed: 22709571
pmcid: 3439334
Siolas, D. & Hannon, G. J. Patient-derived tumor xenografts: transforming clinical samples into mouse models. Cancer Res. 73, 5315–5319 (2013).
pubmed: 23733750
pmcid: 3766500
Tsuchida, Y., Yokomori, K., Iwanaka, T. & Saito, S. Nude mouse xenograft study for treatment of neuroblastoma: effects of chemotherapeutic agents and surgery on tumor growth and cell kinetics. J. Pediatr. Surg. 19, 72–76 (1984).
pubmed: 6583377
Tsuchida, Y., Kanda, N., Shimatake, H., Kaneko, Y. & Notomi, T. Clinical significance of gene amplification studied in human neuroblastoma xenografts: relationship with tumor growth rate, chemotherapeutic sensitivities and levels of neuron-specific enolase. Exp. Cell Biol. 56, 277–284 (1988).
pubmed: 3229554
George, B. A., Yanik, G., Wells, R. J., Martin, L. W., Soukup, S., Ballard, E. T. et al. Growth patterns of human neuroblastoma xenografts and their relationship to treatment outcome. Cancer. 72, 3331–3339 (1993).
pubmed: 8242560
Braekeveldt, N. & Bexell, D. Patient-derived xenografts as preclinical neuroblastoma models. Cell Tissue Res. 372, 233–243 (2018).
pubmed: 28924803
Braekeveldt, N., von Stedingk, K., Fransson, S., Martinez-Monleon, A., Lindgren, D., Axelson, H. et al. Patient-derived xenograft models reveal intratumor heterogeneity and temporal stability in neuroblastoma. Cancer Res. 78, 5958–5969 (2018).
pubmed: 30154149
Braekeveldt, N., Wigerup, C., Gisselsson, D., Mohlin, S., Merselius, M., Beckman, S. et al. Neuroblastoma patient-derived orthotopic xenografts retain metastatic patterns and geno- and phenotypes of patient tumours. Int. J. Cancer 136, E252–E261 (2015).
pubmed: 25220031
Braekeveldt, N., Wigerup, C., Tadeo, I., Beckman, S., Sanden, C., Jonsson, J. et al. Neuroblastoma patient-derived orthotopic xenografts reflect the microenvironmental hallmarks of aggressive patient tumours. Cancer Lett. 375, 384–389 (2016).
pubmed: 27000989
Stewart, E., Federico, S. M., Chen, X., Shelat, A. A., Bradley, C., Gordon, B. et al. Orthotopic patient-derived xenografts of paediatric solid tumours. Nature 549, 96–100 (2017).
pubmed: 28854174
pmcid: 5659286
Stewart, E., Shelat, A., Bradley, C., Chen, X., Federico, S., Thiagarajan, S. et al. Development and characterization of a human orthotopic neuroblastoma xenograft. Dev. Biol. 407, 344–355 (2015).
pubmed: 25863122
pmcid: 4995597
Van Noord, R. A., Thomas, T., Krook, M., Chukkapalli, S., Hoenerhoff, M. J., Dillman, J. R. et al. Tissue-directed implantation using ultrasound visualization for development of biologically relevant metastatic tumor xenografts. In Vivo. 31, 779–791 (2017).
Morton, C. L. & Houghton, P. J. Establishment of human tumor xenografts in immunodeficient mice. Nat. Protoc. 2, 247–250 (2007).
pubmed: 17406581
Read, M., Liu, D., Duong, C. P., Cullinane, C., Murray, W. K., Fennell, C. M. et al. Intramuscular transplantation improves engraftment rates for esophageal patient-derived tumor xenografts. Ann. Surg. Oncol. 23, 305–311 (2016).
pubmed: 25691278
Khanna, C., Jaboin, J. J., Drakos, E., Tsokos, M. & Thiele, C. J. Biologically relevant orthotopic neuroblastoma xenograft models: primary adrenal tumor growth and spontaneous distant metastasis. In Vivo. 16, 77–85 (2002).
pubmed: 12073775
Houghton, P. J., Morton, C. L., Tucker, C., Payne, D., Favours, E., Cole, C. et al. The pediatric preclinical testing program: description of models and early testing results. Pediatr. Blood Cancer 49, 928–940 (2007).
pubmed: 17066459
Attiyeh, E. F., Diskin, S. J., Attiyeh, M. A., Mosse, Y. P., Hou, C., Jackson, E. M. et al. Genomic copy number determination in cancer cells from single nucleotide polymorphism microarrays based on quantitative genotyping corrected for aneuploidy. Genome Res. 19, 276–283 (2009).
pubmed: 19141597
pmcid: 2652209
Ben-David, U., Ha, G., Tseng, Y. Y., Greenwald, N. F., Oh, C., Shih, J. et al. Patient-derived xenografts undergo mouse-specific tumor evolution. Nat. Genet. 49, 1567–1575 (2017).
pubmed: 28991255
pmcid: 5659952
Eirew, P., Steif, A., Khattra, J., Ha, G., Yap, D., Farahani, H. et al. Dynamics of genomic clones in breast cancer patient xenografts at single-cell resolution. Nature 518, 422–426 (2015).
pubmed: 25470049
Shultz, L. D., Lyons, B. L., Burzenski, L. M., Gott, B., Chen, X., Chaleff, S. et al. Human lymphoid and myeloid cell development in NOD/LtSz-scid IL2R gamma null mice engrafted with mobilized human hemopoietic stem cells. J. Immunol. 174, 6477–6489 (2005).
pubmed: 15879151
Ito, R., Katano, I., Kawai, K., Hirata, H., Ogura, T., Kamisako, T. et al. Highly sensitive model for xenogenic GVHD using severe immunodeficient NOG mice. Transplantation 87, 1654–1658 (2009).
pubmed: 19502956
John, T., Yanagawa, N., Kohler, D., Craddock, K. J., Bandarchi-Chamkhaleh, B., Pintilie, M. et al. Characterization of lymphomas developing in immunodeficient mice implanted with primary human non-small cell lung cancer. J. Thorac. Oncol. 7, 1101–1108 (2012).
pubmed: 22617243
Chen, K., Ahmed, S., Adeyi, O., Dick, J. E. & Ghanekar, A. Human solid tumor xenografts in immunodeficient mice are vulnerable to lymphomagenesis associated with Epstein-Barr virus. PLoS One 7, e39294 (2012).
pubmed: 22723990
pmcid: 3377749
Zhang, L., Liu, Y., Wang, X., Tang, Z., Li, S., Hu, Y. et al. The extent of inflammatory infiltration in primary cancer tissues is associated with lymphomagenesis in immunodeficient mice. Sci. Rep. 5, 9447 (2015).
pubmed: 25819560
pmcid: 4377553
Bondarenko, G., Ugolkov, A., Rohan, S., Kulesza, P., Dubrovskyi, O., Gursel, D. et al. Patient-derived tumor xenografts are susceptible to formation of human lymphocytic tumors. Neoplasia 17, 735–741 (2015).
pubmed: 26476081
pmcid: 4611072
Wetterauer, C., Vlajnic, T., Schuler, J., Gsponer, J. R., Thalmann, G. N., Cecchini, M. et al. Early development of human lymphomas in a prostate cancer xenograft program using triple knock-out immunocompromised mice. Prostate 75, 585–592 (2015).
pubmed: 25585936
Choi, Y. Y., Lee, J. E., Kim, H., Sim, M. H., Kim, K. K., Lee, G. et al. Establishment and characterisation of patient-derived xenografts as paraclinical models for gastric cancer. Sci. Rep. 6, 22172 (2016).
pubmed: 26926953
pmcid: 4772087
Mukohyama, J., Iwakiri, D., Zen, Y., Mukohara, T., Minami, H., Kakeji, Y. et al. Evaluation of the risk of lymphomagenesis in xenografts by the PCR-based detection of EBV BamHI W region in patient cancer specimens. Oncotarget 7, 50150–50160 (2016).
pubmed: 27367028
pmcid: 5226574
Thorley-Lawson, D. A. & Gross, A. Persistence of the Epstein-Barr virus and the origins of associated lymphomas. N. Engl. J. Med. 350, 1328–1337 (2004).
pubmed: 15044644
Butler, K. A., Hou, X., Becker, M. A., Zanfagnin, V., Enderica-Gonzalez, S., Visscher, D. et al. Prevention of human lymphoproliferative tumor formation in ovarian cancer patient-derived xenografts. Neoplasia 19, 628–636 (2017).
pubmed: 28658648
pmcid: 5487305
Byrne, F. L., McCarroll, J. A. & Kavallaris, M. Analyses of tumor burden in vivo and metastasis ex vivo using luciferase-expressing cancer cells in an orthotopic mouse model of neuroblastoma. Methods Mol. Biol. 1372, 61–77 (2016).
pubmed: 26530915
Teitz, T., Stanke, J. J., Federico, S., Bradley, C. L., Brennan, R., Zhang, J. et al. Preclinical models for neuroblastoma: establishing a baseline for treatment. PLoS One 6, e19133 (2011).
pubmed: 21559450
pmcid: 3084749
Loh, A. H. P., Stewart, E., Bradley, C. L., Chen, X., Daryani, V., Stewart, C. F. et al. Combinatorial screening using orthotopic patient derived xenograft-expanded early phase cultures of osteosarcoma identify novel therapeutic drug combinations. Cancer Lett. 442, 262–270 (2019).
pubmed: 30395907