Monoclonal Antibody Therapies for High Risk Neuroblastoma

Furman, Wayne L.

doi:10.2147/btt.s267278

Cited by 16 publications

(21 citation statements)

References 137 publications

(127 reference statements)

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“…Survival from high-risk neuroblastoma is improved by monoclonal antibody directed against a cell surface disialoganglioside (GD2) expressed by neuroblasts. 65,66 GD2 is also expressed by nociceptive C-fibers, 67 and resultant acute neuropathic pain can be managed with gabapentin (commenced prior to treatment), supplemented with IV opioids during infusion. In our series, opioid requirements reduced with time as newer protocols were adopted, and lower requirements have also been documented with more recent preparations.…”

Section: Discussionmentioning

confidence: 99%

“…Survival from high‐risk neuroblastoma is improved by monoclonal antibody directed against a cell surface disialoganglioside (GD2) expressed by neuroblasts 65,66 . GD2 is also expressed by nociceptive C‐fibers, 67 and resultant acute neuropathic pain can be managed with gabapentin (commenced prior to treatment), supplemented with IV opioids during infusion.…”

Section: Discussionmentioning

confidence: 99%

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Intravenous opioids for chemotherapy‐induced severe mucositis pain in children: Systematic review and single‐center case series of management with patient‐ or nurse‐controlled analgesia (PCA/NCA)

Walker

Selers

Jay

et al. 2021

Pediatric Anesthesia

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Background: Chemotherapy-induced oral mucositis can result in severe pain.Intravenous (IV) opioids are recommended, but management protocols vary. We systematically reviewed studies reporting IV opioid use for pain related to chemotherapyinduced severe oral mucositis in children and conducted a large single-center case series.Methods: Ovid MEDLINE, PubMed, and Cochrane databases were searched for studies reporting IV opioid duration and/or dose requirements for severe mucositis.Secondly, our pain service database was interrogated to describe episodes of opioid administration by patient-or nurse-controlled analgesia (PCA/NCA) for children with mucositis and cancer treatment-related pain.Results: Seventeen studies (six randomized trials, two prospective observational, three retrospective cohort, six retrospective case series) included IV opioid in 618 patients (age 0.3-22.3 years), but reported parameters varied. Mucositis severity and chemotherapy indication influenced IV opioid requirements, with duration ranging from 3 to 68 days and variable dose trajectories (hourly morphine or equivalent 0-97 mcg/kg/h). Our 7-year series included PCA/NCA for 364 episodes of severe mucositis (302 patients; age 0.12-17.2 years). Duration ranged from 1 to 107 days and dose requirements in the first 3 days from 1 to 110 mcg/kg/h morphine. Longer PCA/ NCA duration was associated with: higher initial morphine requirements (ρ = 0.46 [95% CI 0.35, 0.57]); subsequent increased pain and need for ketamine co-analgesia (118/364 episodes with opioid/ketamine 13.9 [9.8-22.2] days vs opioid alone 6.0 [3.9-10.8] days; median [IQR]); but not with age or sex.Conclusions: Management of severe mucositis pain can require prolonged IV opioid therapy. Individual and treatment-related variability in analgesic requirements highlight the need for regular review, titration, and management by specialist services.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Intravenous opioids for chemotherapy‐induced severe mucositis pain in children: Systematic review and single‐center case series of management with patient‐ or nurse‐controlled analgesia (PCA/NCA)

Walker

Selers

Jay

et al. 2021

Pediatric Anesthesia

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“…Currently, there are several ongoing clinical trials involving the use of various forms of anti-GD2, and they have all yielded reasonably good results [88]. However, despite the use of anti-GD2, almost 50% of patients still relapsed.…”

Section: Future Prospectivementioning

confidence: 99%

Anti-GD2 Directed Immunotherapy for High-Risk and Metastatic Neuroblastoma

Chan

2022

Biomolecules

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Neuroblastoma is one of the few childhood cancers that carries a tumor-specific antigen in the form of a glycolipid antigen known as GD2. It has restricted expression in normal tissue, such as peripheral afferent nerves. Monoclonal antibodies targeting GD2 have been applied clinically to high-risk neuroblastoma with significant success. However, there are different anti-GD2 products and administration regimens. For example, anti-GD2 has been used in combination with chemotherapy during the induction phase or with retinoic acid during the maintenance stage. Regimens also vary in the choice of whether to add cytokines (i.e., IL-2, GMCSF, or both). Furthermore, the addition of an immune enhancer, such as β-glucan, or allogeneic natural killer cells also becomes a confounder in the interpretation. The question concerning which product or method of administration is superior remains to be determined. So far, most studies agree that adding anti-GD2 to the conventional treatment protocol can achieve better short- to intermediate-term event-free and overall survival, but the long-term efficacy remains to be verified. How to improve its efficacy is another challenge. Late relapse and central nervous system metastasis have emerged as new problems. The methods to overcome the mechanisms related to immune evasion or resistance to immunotherapy represent new challenges to be resolved. The newer anti-GD2 strategies, such as bispecific antibody linking of anti-GD2 with activated T cells or chimeric antigen receptor T cells, are currently under clinical trials, and they may become promising alternatives. The use of anti-GD2/GD3 tumor vaccine is a novel and potential approach to minimizing late relapse. How to induce GD2 expression from tumor cells using the epigenetic approach is a hot topic nowadays. We expect that anti-GD2 treatment can serve as a model for the use of monoclonal antibody immunotherapy against cancers in the future.

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“…To date, the most effective treatment for patients with high-risk neuroblastoma is achieved through immunotherapy, which is based on GD2 ganglioside-specific antibodies combined with multimodal treatment (Kholodenko et al, 2018;Furman, 2021;Morandi et al, 2021). The GD2 ganglioside is a well-established molecular target in neuroblastoma due to its high expression in neuroblastic cells (Terzic et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Apoptosis is responsible for the cytotoxic effects of anti-GD2 ganglioside antibodies and aurora A kinase inhibitors on human neuroblastoma cells

et al. 2022

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In recent years, immunotherapy has been identified as an effective treatment method for high-risk neuroblastoma. A previous study demonstrated that an anti-GD2 ganglioside (GD2) mouse 14G2a monoclonal antibody (mAb) combined with a small molecule, i.e., an aurora A kinase inhibitor (MK-5108), significantly increased cytotoxicity against human neuroblastoma cells, as compared to monotherapy. This study aimed to demonstrate the mechanism of neuroblastoma cell death in vitro following the addition of an anti-GD2 human-mouse chimeric ch14.18/CHO mAb (presently used in clinics) and two aurora A inhibitors (MK-5108 and MK-8745). The effects of the aforementioned agents on neuroblastoma cells were determined by measuring the level of ATP, the level of apoptotic and necroptotic markers, and the activity of caspase 3/7. The results revealed that the ch14.18/CHO mAb decreased cellular ATP levels in the IMR-32 and CHP-134 neuroblastoma cell lines, similarly to the 14G2a mAb. Regarding ch14.18/CHO mAb treated IMR-32 cells, the observed cytotoxic effect was concomitant with induced caspase 3 cleavage, which indicated the induction of apoptosis in IMR-32 cells, but not in CHP-134 cells. Furthermore, the MK-5108 inhibitor induced apoptosis, as indicated by the increased cleavage of caspase 3 and increased activity of caspase 3/7. However, the presence of necroptosis was ruled out in MK-5108-treated IMR-32 and CHP-134 cells. In summary, the effects of the combination of ch14.18/CHO mAb and aurora A kinase inhibitors (MK-5108 and MK-8745) were shown to enhance apoptosis in IMR-32 cells compared to when used individually.

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Monoclonal Antibody Therapies for High Risk Neuroblastoma

Cited by 16 publications

References 137 publications

Intravenous opioids for chemotherapy‐induced severe mucositis pain in children: Systematic review and single‐center case series of management with patient‐ or nurse‐controlled analgesia (PCA/NCA)

Intravenous opioids for chemotherapy‐induced severe mucositis pain in children: Systematic review and single‐center case series of management with patient‐ or nurse‐controlled analgesia (PCA/NCA)

Anti-GD2 Directed Immunotherapy for High-Risk and Metastatic Neuroblastoma

Apoptosis is responsible for the cytotoxic effects of anti-GD2 ganglioside antibodies and aurora A kinase inhibitors on human neuroblastoma cells

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