Immunotherapeutic Strategies for Neuroblastoma: Present, Past and Future

Morandi, Fabio; Sabatini, Federica; Podestà, Marina; Airoldi, Irma

doi:10.3390/vaccines9010043

Cited by 31 publications

(27 citation statements)

References 138 publications

(194 reference statements)

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“…Patients were grouped and staged according to the INRG classification and staging system (19,20). The clinical stage of the patients was confirmed by fluorodeoxyglucose positron emission tomography, computerized tomography and/or metaiodobenzylguanidine (MIBG) scan in addition to other methods such as bone marrow biopsy, bone scan, cranial magnetic resonance imaging and ultrasonic examination (18).…”

Section: Patientsmentioning

confidence: 99%

Impact of 11q Loss of Heterozygosity Status on the Response of High-Risk Neuroblastoma With MYCN Amplification to Neoadjuvant Chemotherapy

Duan

et al. 2022

Front. Pediatr.

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PurposeThe aim of this study was to investigate whether 11q loss of heterozygosity (LOH) aberration would impact the response of the primary tumor to neoadjuvant chemotherapy or to the degree of surgical resection in neuroblastoma (NB) patients with MYCN amplification.MethodsThe clinical data of 42 NB patients with MYCN amplification who were newly diagnosed and received treatments at our hospital from 2011 to 2020 were retrospectively analyzed. According to the results of the segmental chromosome aberration analysis, the patients enrolled were assigned to an 11qLOH positive group and an 11qLOH negative group.ResultsThere was no significant difference in the mean number of chemotherapy courses completed before surgery between the 11qLOH positive and 11qLOH negative groups (p = 0.242). Each of the 42 patients had metaiodobenzylguanidine (MIBG) scans both before and after neoadjuvant chemotherapy. The percentage of patients who had a clinical MIBG change in the 11qLOH positive group was lower than the percentage in the 11qLOH negative group (27.27 vs. 66.67%, p = 0.030). The 11qLOH negative group seemed to have a higher rate of surgical resection (≥90%); however, the difference between the two groups was not statistically significant (p = 0.088). Furthermore, the 11qLOH negative group did not show significantly superior event-free survival and overall survival rates compared with the 11qLOH positive group.ConclusionsThis study showed that patients with NB and MYCN amplification in combination with 11qLOH might be less likely to respond to neoadjuvant chemotherapy when compared with patients with NB and MYCN amplification without 11qLOH.

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Section: Patientsmentioning

confidence: 99%

Impact of 11q Loss of Heterozygosity Status on the Response of High-Risk Neuroblastoma With MYCN Amplification to Neoadjuvant Chemotherapy

Duan

et al. 2022

Front. Pediatr.

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“…A recent update from a phase III trial (HR-NBL1/SIOPEN) demonstrated no additional benefit and added toxicity with interleukin (IL)-2 when given with dinutuximab to patients with high-risk neuroblastoma [19], leading to discontinuation of use of IL-2 in similar COG protocols. Other recent advances with anti-GD2 antibodies in neuroblastoma are reviewed elsewhere [20].…”

Section: Disialoganglioside Gd2mentioning

confidence: 99%

Immunotherapies for Pediatric Solid Tumors: A Targeted Update

Gupta

Cripe

2021

Pediatr Drugs

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There are encouraging signs in our collective progress to leverage the immune system to treat pediatric cancers. Here, we summarize interim successes in cancer immunotherapy and opportunities to translate from the adult world to pediatrics, and highlight challenges that could benefit from additional development, focusing on solid tumors. Just a decade ago, other than antibodies targeting disialoganglioside (GD2) in neuroblastoma, pediatric cancer immunotherapy was mostly relegated to obscure preclinical studies in a few academic labs. Today there are numerous clinical trials of a variety of antibody, cellular, gene, and viral therapies and vaccines designed to either promote antitumor immunity or specifically attack validated immunotherapy targets. Understanding those targets and their pediatric relevance is paramount. While much work is underway to evaluate the utility of numerous immunologic targets, the lack of regulatory approvals is emblematic of the challenges that remain. Herein we focus our review on the most promising targeted immunotherapies in clinical trials for children. Key PointsTreatment of pediatric solid tumors is starting to benefit from a variety of cell-surface targets and new approaches to attack those targets.The most promising of these targets include: immune checkpoints, GD2, B7-H3, HER2, and CD47. Future directions will likely include combinations of therapies, biomarkers to assess success, the creation of more antibody-drug conjugates, and further breakdown of regulatory barriers.

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“…In recent years, harnessing the body's own immune system via immunotherapies has proven to be an effective strategy in many cancer types, [ 3 ] and addition of immunotherapy agents to existing cytotoxic regimens has demonstrated improved outcomes for patients with neuroblastoma. [ 3 – 6 ]…”

Section: Introductionmentioning

confidence: 99%

Dinutuximab beta in the treatment of high-risk neuroblastoma

Achbergerová¹,

Hederová²,

Hrašková³

et al. 2022

Medicine

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Despite therapeutic advances, high-risk neuroblastoma is still associated with a poor long-term prognosis. Immunotherapy with the anti-GD2 antibody dinutuximab beta has recently been added to the standard of care for patients with high-risk neuroblastoma in our center in Bratislava, and our initial experience with dinutuximab beta has been reported previously. Here we provide a follow-up on the outcomes of 7 patients who were treated with dinutuximab beta under clinical practice conditions at our center. Medical records of 31 patients diagnosed with neuroblastoma between 2017 and 2020 at the Children's Hematology and Oncology Clinic in Bratislava were retrospectively reviewed and 7 patients with high-risk neuroblastoma who were treated with dinutuximab beta were identified. All 7 patients received dinutuximab beta as continuous infusion over 10 days at a dose of 10 mg/m 2 /day for 5 cycles, following induction and consolidation therapy. Supportive therapy was administered to manage adverse events. Clinical outcomes and treatment tolerance were evaluated. Six of 7 patients treated with dinutuximab beta achieved complete remission, with a median duration of response of 21.5 months as of January 2022, and 1 displayed stable disease 21 months after treatment completion. Treatment was tolerable in most patients, with the majority of adverse events managed with supportive care. Dinutuximab beta is an effective immunotherapy for patients with high-risk neuroblastoma in routine clinical practice when coupled with optimal supportive management of adverse events.

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Immunotherapeutic Strategies for Neuroblastoma: Present, Past and Future

Cited by 31 publications

References 138 publications

Impact of 11q Loss of Heterozygosity Status on the Response of High-Risk Neuroblastoma With MYCN Amplification to Neoadjuvant Chemotherapy

Impact of 11q Loss of Heterozygosity Status on the Response of High-Risk Neuroblastoma With MYCN Amplification to Neoadjuvant Chemotherapy

Immunotherapies for Pediatric Solid Tumors: A Targeted Update

Dinutuximab beta in the treatment of high-risk neuroblastoma

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