Mouse models of high-risk neuroblastoma

Kamili, Alvin; Atkinson, Caroline; Trahair, Toby N.; Fletcher, Jamie I.

doi:10.1007/s10555-020-09855-0

Cited by 22 publications

(25 citation statements)

References 122 publications

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“…In addition, the primary NB cells were cultivated for a low number of passages in vitro before xenotransplantation, and NB-PDX harbor several additional SCA alterations as compared to NB tumors derived from the corresponding patients, which may affect their phenotypic characteristics or biological properties. Moreover, these PDX models may not fully reflect the exact NB microenvironment, which would have been reproduced in a more appropriate manner though orthotopic injection into the adrenal glands and/or by using small fragments of NB primary tumors which contains the additional stromal cells that represent key players in tumor progression [25][26][27]. However, despite these limitations, the NB-PDX models closely mimic the metabolism of catecholamine as observed in patients, regarding not only plasma levels of MNs, but also intratumoral CAT and MN concentrations, as well as mRNA expression levels of gene involved in CAT metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, levels of MNs in mice models are also very likely to reflect the progression of tumor. Several models of NB in mice have been established [25,27]. Apart from deciphering the molecular and genetic aspects of the tumors, as PNMT downregulation described in this report, NB preclinical models are also widely used for the assessment of new treatment strategies [25,27].…”

Section: Discussionmentioning

confidence: 99%

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The noradrenergic profile of plasma metanephrine in neuroblastoma patients is reproduced in xenograft mice models and arise from PNMT downregulation

et al. 2021

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The noradrenergic profile of plasma metanephrine in neuroblastoma patients is reproduced in xenograft mice models and arise from PNMT downregulation

et al. 2021

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“…5 ). Additional studies are necessary to elucidate the underlying immunological mechanisms that elicit these protective responses, and these are the focus of several ongoing studies in our group, including in models of high-risk and metastatic neuroblastoma [ 48 , 49 ]. To summarize, we have demonstrated that engineered nanoparticles can serve as an effective platform for priming and/or activating an antitumor immune response.…”

Section: Discussionmentioning

confidence: 99%

CpG-coated prussian blue nanoparticles-based photothermal therapy combined with anti-CTLA-4 immune checkpoint blockade triggers a robust abscopal effect against neuroblastoma

Cano‐Mejia

Shukla

Ledezma

et al. 2020

Translational Oncology

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High-risk neuroblastoma, which is associated with regional and systemic metastasis, is a leading cause of cancer-related mortality in children. Responding to this need for novel therapies for high-risk patients, we have developed a “nanoimmunotherapy,” which combines photothermal therapy (PTT) using CpG oligodeoxynucleotide-coated Prussian blue nanoparticles (CpG-PBNPs) combined with anti-CTLA-4 (aCTLA-4) immunotherapy. Our in vitro studies demonstrate that in addition to causing ablative tumor cell death, our nanoimmunotherapy alters the surface levels of co-stimulatory, antigen-presenting, and co-inhibitory molecules on neuroblastoma tumor cells. When administered in a syngeneic, murine model of neuroblastoma bearing synchronous Neuro2a tumors, the CpG-PBNP-PTT plus aCTLA-4 nanoimmunotherapy elicits complete tumor regression in both primary (CpG-PBNP-PTT-treated) and secondary tumors, and long-term survival in a significantly higher proportion (55.5%) of treated-mice compared with the controls. Furthermore, the surviving, nanoimmunotherapy-treated animals reject Neuro2a rechallenge, suggesting that the therapy generates immunological memory. Additionally, the depletion of CD4 + , CD8 + , and NK + populations abrogate the observed therapeutic responses of the nanoimmunotherapy. These findings demonstrate the importance of concurrent PTT-based cytotoxicity and the antitumor immune effects of PTT, CpG, and aCTLA-4 in generating a robust abscopal effect against neuroblastoma.

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“…Here, we present data comparing the most widely used immunocompetent murine models and their ability to model human NB disease. However, xenograph models, using human tissue or cell lines are another model which can be utilized 15,36,[53][54][55][56] . Until recently these models mainly used immunompromised mice and therefore it would be difficult to study tumor immunology and immunotherapeutics.…”

Section: Discussionmentioning

confidence: 99%

“…In summary, due to the spontaneity and location of TH-MYCN tumor development, together with its histology, immune infiltrates and MHC class I expression we believe this model currently best represents the immune environment of NB, although this model does fail to recapitulate bone metastasis and complex heterogeneity as seen in human MYCN amplified neuroblastoma 15,54 . However, pre-clinical testing in this model requires maintenance of a large colony of transgenic mice.…”

Section: Discussionmentioning

confidence: 99%

Immune characterization of pre-clinical murine models of neuroblastoma

Webb

Lanati

Wareham

et al. 2020

Sci Rep

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Immunotherapy offers a potentially less toxic, more tumor-specific treatment for neuroblastoma than conventional cytotoxic therapies. Accurate and reproducible immune competent preclinical models are key to understanding mechanisms of action, interactions with other therapies and mechanisms of resistance to immunotherapy. Here we characterized the tumor and splenic microenvironment of two syngeneic subcutaneous (NXS2 and 9464D), and a spontaneous transgenic (TH-MYCN) murine model of neuroblastoma, comparing histological features and immune infiltrates to previously published data on human neuroblastoma. Histological sections of frozen tissues were stained by immunohistochemistry and immunofluorescence for immune cell markers and tumor architecture. Tissues were dissociated by enzymatic digestion, stained with panels of antibodies to detect and quantify cancer cells, along with lymphocytic and myeloid infiltration by flow cytometry. Finally, we tested TH-MYCN mice as a feasible model for immunotherapy, using prior treatment with cyclophosphamide to create a therapeutic window of minimal residual disease to favor host immune development. Immune infiltration differed significantly between all the models. TH-MYCN tumors were found to resemble immune infiltration in human tumors more closely than the subcutaneous models, alongside similar GD2 and MHC class I expression. Finally, TH-MYCN transgenic mice were administered cyclophosphamide alone or in combination with an anti-GD2 or anti-4-1BB monoclonal antibody, which resulted in increase in survival in both combination therapies. The TH-MYCN transgenic mouse is a promising in vivo model for testing immunotherapy compounds and combination therapy in a preclinical setting.

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Mouse models of high-risk neuroblastoma

Cited by 22 publications

References 122 publications

The noradrenergic profile of plasma metanephrine in neuroblastoma patients is reproduced in xenograft mice models and arise from PNMT downregulation

The noradrenergic profile of plasma metanephrine in neuroblastoma patients is reproduced in xenograft mice models and arise from PNMT downregulation

CpG-coated prussian blue nanoparticles-based photothermal therapy combined with anti-CTLA-4 immune checkpoint blockade triggers a robust abscopal effect against neuroblastoma

Immune characterization of pre-clinical murine models of neuroblastoma

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