Accelerating development of high-risk neuroblastoma patient-derived xenograft models for preclinical testing and personalised therapy.

Abstract

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.

• Authors: Alvin Kamili, Andrew J Gifford, Nancy Li, Chelsea Mayoh, Shu-Oi Chow, Timothy W Failes, Georgina L Eden, Roxanne Cadiz, Jinhan Xie, Robyn E Lukeis, Murray D Norris, Michelle Haber, Geoffrey B McCowage, Greg M Arndt, Toby N Trahair, Jamie I Fletcher
• Journal: British journal of cancer (Br J Cancer) Vol. 122 Issue 5 Pg. 680-691 (03 2020) ISSN: 1532-1827 [Electronic] England
• PMID: 31919402 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Topics

• Animals
• Feasibility Studies
• Female
• Humans
• Immunohistochemistry
• Mice
• Mice, Inbred NOD
• Neoplasm Transplantation (methods)
• Neuroblastoma (genetics, pathology, therapy)
• Precision Medicine (methods)
• Random Allocation
• T-Lymphocytes (immunology, pathology)
• Xenograft Model Antitumor Assays (methods)