Immune Response and Outcome of High-Risk Neuroblastoma Patients Immunized with Anti-Idiotypic Antibody Ganglidiomab: Results from Compassionate-Use Treatments

Klingel, Leah; Siebert, Nikolai; Troschke-Meurer, Sascha; Zumpe, Maxi; Ehlert, Karoline; Huber, Stefanie; Loibner, Hans; Mutschlechner, Oliver; Lode, Holger N.

doi:10.3390/cancers14235802

Cited by 3 publications

(3 citation statements)

References 33 publications

(43 reference statements)

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“…134 Another investigational strategy seeks to exploit the anti-idiotypic response to anti-GD2 mAbs whereby anti-GD2 anti-idiotype antibodies are being developed and investigated for use as anti-neuroblastoma vaccines. [135][136][137][138] Some investigational anti-GD2-based therapies have also shown promise in neuroblastoma when used in combination with GM-CSF (Table S3). Anti-GD2 therapies with or without GM-CSF are being explored in other disease states such as osteosarcoma [139][140][141] and breast cancer.…”

Section: Discussionmentioning

confidence: 99%

“…Phase 2 data indicate that GD2/GD3 vaccine plus β‐glucan elicits anti‐GD2 antibody responses in patients with HR‐NB, 132,133 and an ongoing trial (NCT04936529) is investigating whether addition of GM‐CSF as a vaccine adjuvant will enhance seroconversion rates 134 . Another investigational strategy seeks to exploit the anti‐idiotypic response to anti‐GD2 mAbs whereby anti‐GD2 anti‐idiotype antibodies are being developed and investigated for use as anti‐neuroblastoma vaccines 135–138 . Some investigational anti‐GD2‐based therapies have also shown promise in neuroblastoma when used in combination with GM‐CSF (Table S3).…”

Section: Discussionmentioning

confidence: 99%

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GM‐CSF, G‐CSF or no cytokine therapy with anti‐GD2 immunotherapy for high‐risk neuroblastoma

Mora,

Modak,

Kinsey

et al. 2023

Intl Journal of Cancer

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Colony‐stimulating factors have been shown to improve anti‐disialoganglioside 2 (anti‐GD2) monoclonal antibody response in high‐risk neuroblastoma by enhancing antibody‐dependent cell‐mediated cytotoxicity (ADCC). A substantial amount of research has focused on recombinant human granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) as an adjuvant to anti‐GD2 monoclonal antibodies. There may be a disparity in care among patients as access to GM‐CSF therapy and anti‐GD2 monoclonal antibodies is not uniform. Only select countries have approved these agents for use, and even with regulatory approvals, access to these agents can be complex and cost prohibitive. This comprehensive review summarizes clinical data regarding efficacy and safety of GM‐CSF, recombinant human granulocyte colony‐stimulating factor (G‐CSF) or no cytokine in combination with anti‐GD2 monoclonal antibodies (ie, dinutuximab, dinutuximab beta or naxitamab) for immunotherapy of patients with high‐risk neuroblastoma. A substantial body of clinical data support the immunotherapy combination of anti‐GD2 monoclonal antibodies and GM‐CSF. In contrast, clinical data supporting the use of G‐CSF are limited. No formal comparison between GM‐CSF, G‐CSF and no cytokine has been identified. The treatment of high‐risk neuroblastoma with anti‐GD2 therapy plus GM‐CSF is well established. Suboptimal efficacy outcomes with G‐CSF raise concerns about its suitability as an alternative to GM‐CSF as an adjuvant in immunotherapy for patients with high‐risk neuroblastoma. While programs exist to facilitate obtaining GM‐CSF and anti‐GD2 monoclonal antibodies in regions where they are not commercially available, continued work is needed to ensure equitable therapeutic options are available globally.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

GM‐CSF, G‐CSF or no cytokine therapy with anti‐GD2 immunotherapy for high‐risk neuroblastoma

Mora,

Modak,

Kinsey

et al. 2023

Intl Journal of Cancer

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“…Clinical use of 1A7 showed no toxic effects, but objective responses were minimal (255). However, a ganglidiomab antibody against anti-GD2 antibody family 14.18 was later developed, which induced a humoral response in murine models (257) and among patients after therapy with anti-GD2 mAbs, demonstrating good tolerability without significant side effects (258). The development of anti-Id antibodies mimicking human and mouse GD2 ganglidiximab, which is capable of mediating ADCC and CDC, and which may be useful for tailoring humoral responses to paratopic regions mimicking GD2, was also reported (259).…”

Section: Anti-gd2 and Idiotopic Vaccinementioning

confidence: 99%

GD2-targeting therapy: a comparative analysis of approaches and promising directions

Philippova,

Shevchenko,

Sennikov

2024

Front. Immunol.

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Disialoganglioside GD2 is a promising target for immunotherapy with expression primarily restricted to neuroectodermal and epithelial tumor cells. Although its role in the maintenance and repair of neural tissue is well-established, its functions during normal organism development remain understudied. Meanwhile, studies have shown that GD2 plays an important role in tumorigenesis. Its functions include proliferation, invasion, motility, and metastasis, and its high expression and ability to transform the tumor microenvironment may be associated with a malignant phenotype. Structurally, GD2 is a glycosphingolipid that is stably expressed on the surface of tumor cells, making it a suitable candidate for targeting by antibodies or chimeric antigen receptors. Based on mouse monoclonal antibodies, chimeric and humanized antibodies and their combinations with cytokines, toxins, drugs, radionuclides, nanoparticles as well as chimeric antigen receptor have been developed. Furthermore, vaccines and photoimmunotherapy are being used to treat GD2-positive tumors, and GD2 aptamers can be used for targeting. In the field of cell therapy, allogeneic immunocompetent cells are also being utilized to enhance GD2 therapy. Efforts are currently being made to optimize the chimeric antigen receptor by modifying its design or by transducing not only αβ T cells, but also γδ T cells, NK cells, NKT cells, and macrophages. In addition, immunotherapy can combine both diagnostic and therapeutic methods, allowing for early detection of disease and minimal residual disease. This review discusses each immunotherapy method and strategy, its advantages and disadvantages, and highlights future directions for GD2 therapy.

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Mimicry of Tumour-Associated Carbohydrates: Is It a Promising Option for Cancer Treatment?

Segatori

Ferreira

Rojo

et al. 2023

Immuno

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Modulation of the immune system has been demonstrated as a powerful approach to treating cancer. Immunotherapies are generally classified as active or passive according to their ability to trigger the immune system. During the last decades, information regarding the relevance of aberrant glycosylation as a major player in tumour biology encouraged expectations for the development of new therapeutic strategies directed at glycans. Several tumour-associated carbohydrate antigens (TACAs) have been identified and validated as suitable immunotherapeutic targets, leading to promising therapeutic developments. It is known that TACAs are poorly immunogenic since they are unable to trigger a proper immune response. Given that they are not presented by major histocompatibility complex (MHC) molecules and that they induce immune tolerance, the development of active immunotherapeutic strategies against TACAs is a real challenge. However, antitumor strategies based on mimetics of TACAs have been developed and show promising results. Active immunotherapies based on TACAs mimicry can currently be grouped into strategies based on the use of mimetic peptides and anti-idiotype (Id) antibodies. In this review, we discussed the scientific basis on which these strategies are based and the available therapeutic options that have shown the best results in preclinical studies and in clinical practice.

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Immune Response and Outcome of High-Risk Neuroblastoma Patients Immunized with Anti-Idiotypic Antibody Ganglidiomab: Results from Compassionate-Use Treatments

Cited by 3 publications

References 33 publications

GM‐CSF, G‐CSF or no cytokine therapy with anti‐GD2 immunotherapy for high‐risk neuroblastoma

GM‐CSF, G‐CSF or no cytokine therapy with anti‐GD2 immunotherapy for high‐risk neuroblastoma

GD2-targeting therapy: a comparative analysis of approaches and promising directions

Mimicry of Tumour-Associated Carbohydrates: Is It a Promising Option for Cancer Treatment?

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