Targeted Doxorubicin-Loaded Bacterially Derived Nano-Cells for the Treatment of Neuroblastoma

Sagnella, Sharon M.; Trieu, Jennifer; Brahmbhatt, Himanshu; MacDiarmid, Jennifer; Macmillan, Alexander; Whan, Renée; Fife, Christopher M.; McCarroll, Joshua A.; Gifford, Andrew J.; Ziegler, David S.; Kavallaris, Maria

doi:10.1158/1535-7163.mct-17-0738

Cited by 36 publications

(20 citation statements)

References 18 publications

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“…The authors demonstrated that the EGFR-targeted nanocells enhanced penetrance of doxorubicin compared to non-targeted doxorubicin loaded nanocells and doxorubicin without a delivery vehicle, resulting in increased apoptosis. These findings were confirmed in an orthotopic xenograft model [156].…”

Section: D In Vitro Models: Spheroidsupporting

confidence: 59%

Developing preclinical models of neuroblastoma: driving therapeutic testing

Ornell

Coburn

2019

BMC biomed eng

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Despite advances in cancer therapeutics, particularly in the area of immuno-oncology, successful treatment of neuroblastoma (NB) remains a challenge. NB is the most common cancer in infants under 1 year of age, and accounts for approximately 10% of all pediatric cancers. Currently, children with highrisk NB exhibit a survival rate of 40-50%. The heterogeneous nature of NB makes development of effective therapeutic strategies challenging. Many preclinical models attempt to mimic the tumor phenotype and tumor microenvironment. In vivo mouse models, in the form of genetic, syngeneic, and xenograft mice, are advantageous as they replicated the complex tumor-stroma interactions and represent the gold standard for preclinical therapeutic testing. Traditional in vitro models, while high throughput, exhibit many limitations. The emergence of new tissue engineered models has the potential to bridge the gap between in vitro and in vivo models for therapeutic testing. Therapeutics continue to evolve from traditional cytotoxic chemotherapies to biologically targeted therapies. These therapeutics act on both the tumor cells and other cells within the tumor microenvironment, making development of preclinical models that accurately reflect tumor heterogeneity more important than ever. In this review, we will discuss current in vitro and in vivo preclinical testing models, and their potential applications to therapeutic development.

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Section: D In Vitro Models: Spheroidsupporting

confidence: 59%

Developing preclinical models of neuroblastoma: driving therapeutic testing

Ornell

Coburn

2019

BMC biomed eng

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“…Between them, the use of hyperosmotic solutions [56], FUS [155], biodegradable implants [156], and CED [157] are extensively used and/or investigated in the clinic for their safety and efficacy. On the other hand, to our knowledge, only one model of targeted nanoparticle is under investigation in humans for the treatment of GBM [158]. While these strategies were shown to be effective, currently they can increase overall patient survival only by a few weeks.…”

Section: Discussionmentioning

confidence: 99%

Established and Emerging Strategies for Drug Delivery Across the Blood-Brain Barrier in Brain Cancer

et al. 2019

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Brain tumors are characterized by very high mortality and, despite the continuous research on new pharmacological interventions, little therapeutic progress has been made. One of the main obstacles to improve current treatments is represented by the impermeability of the blood vessels residing within nervous tissue as well as of the new vascular net generating from the tumor, commonly referred to as blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB), respectively. In this review, we focused on established and emerging strategies to overcome the blood-brain barrier to increase drug delivery for brain cancer. To date, there are three broad strategies being investigated to cross the brain vascular wall and they are conceived to breach, bypass, and negotiate the access to the nervous tissue. In this paper, we summarized these approaches highlighting their working mechanism and their potential impact on the quality of life of the patients as well as their current status of development.

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“…Another phase 1 study is testing an EGFR-directed mitoxantrone-loaded EDV (EEDVSMit) in children with r/r solid tumors (NCT02687386). A third clinical trial utilized EGFR(V)-EDV-Dox in patients with recurrent glioblastoma (NCT02766699), after it had shown significant prolongation of overall survival in two orthotopic human neuroblastoma xenograft models [ 192 ]. Eight of 14 patients completed one cycle, four more than one cycle of therapy; median PFS was 1.6 months, 2/14 patients had a PFS >6 months, and median OS was 9.7 months.…”

Section: Payload Delivery Using Multispecific Constructsmentioning

confidence: 99%

Principles and Current Clinical Landscape of Multispecific Antibodies against Cancer

Elshiaty

Schindler

Christopoulos

2021

IJMS

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Building upon the resounding therapeutic success of monoclonal antibodies, and supported by accelerating progress in engineering methods, the field of multispecific therapeutic antibodies is growing rapidly. Over 140 different molecules are currently in clinical testing, with excellent results in recent phase 1–3 clinical trials for several of them. Multivalent bispecific IgG-modified formats predominate today, with a clear tendency for more target antigens and further increased valency in newer constructs. The strategies to augment anticancer efficacy are currently equally divided between disruption of multiple surface antigens, and additional redirection of cytotoxic T or NK lymphocytes against the tumor. Both effects complement other modern modalities, such as tyrosine kinase inhibitors and adoptive cell therapies, with which multispecifics are increasingly applied in combination or merged, for example, in the form of antibody producing CAR-T cells and oncolytics. While mainly focused on B-cell malignancies early on, the contemporary multispecific antibody sector accommodates twice as many trials against solid compared to hematologic cancers. An exciting emerging prospect is the targeting of intracellular neoantigens using T-cell receptor (TCR) fusion proteins or TCR-mimic antibody fragments. Considering the fact that introduction of PD-(L)1 inhibitors only a few years ago has already facilitated 5-year survival rates of 30–50% for per se highly lethal neoplasms, such as metastatic melanoma and non-small-cell lung carcinoma, the upcoming enforcement of current treatments with “next-generation” immunotherapeutics, offers a justified hope for the cure of some advanced cancers in the near future.

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Targeted Doxorubicin-Loaded Bacterially Derived Nano-Cells for the Treatment of Neuroblastoma

Cited by 36 publications

References 18 publications

Developing preclinical models of neuroblastoma: driving therapeutic testing

Developing preclinical models of neuroblastoma: driving therapeutic testing

Established and Emerging Strategies for Drug Delivery Across the Blood-Brain Barrier in Brain Cancer

Principles and Current Clinical Landscape of Multispecific Antibodies against Cancer

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