Enhancement of antibody-dependent cytotoxicity with a chimeric anti-GD2 antibody.

Mueller, Barbara M.; Romerdahl, Cynthia A.; Gillies, Stephen D.; Reisfeld, R A

doi:10.4049/jimmunol.144.4.1382

Cited by 159 publications

(9 citation statements)

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“…Although the chemotherapy backbone was identical and the major prognostic factors of our patient populations were comparable with those of ANBL02P1, 14 ANBL0532, 15 and ANBL12P1 25 (Appendix Table A1), several other differences in therapy might have contributed to the excellent NB2012 response rates. For example, GM-CSF was used during induction chemoimmunotherapy, rather than filgrastim, both for its ability to enhance ADCC 33,34 and for primary prophylaxis of febrile neutropenia. 35 Additionally, low-dose IL-2 was used for its ability to enhance ADCC.…”

Section: Discussionmentioning

confidence: 99%

Improved Outcome in Children With Newly Diagnosed High-Risk Neuroblastoma Treated With Chemoimmunotherapy: Updated Results of a Phase II Study Using hu14.18K322A

Furman

McCarville

Shulkin

et al. 2022

JCO

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PURPOSE We evaluated whether combining a humanized antidisialoganglioside monoclonal antibody (hu14.18K322A) throughout therapy improves early response and outcomes in children with newly diagnosed high-risk neuroblastoma. PATIENTS AND METHODS We conducted a prospective, single-arm, three-stage, phase II clinical trial. Six cycles of induction chemotherapy were coadministered with hu14.18K322A, granulocyte-macrophage colony-stimulating factor (GM-CSF), and low-dose interleukin-2 (IL-2). The consolidation regimen included busulfan and melphalan. When available, an additional cycle of parent-derived natural killer cells with hu14.18K322A was administered during consolidation (n = 31). Radiation therapy was administered at the end of consolidation. Postconsolidation treatment included hu14.18K322A, GM-CSF, IL-2, and isotretinoin. Early response was assessed after the first two cycles of induction therapy. End-of-induction response, event-free survival (EFS), and overall survival (OS) were evaluated. RESULTS Sixty-four patients received hu14.18K322A with induction chemotherapy. This regimen was well tolerated, with continuous infusion narcotics. Partial responses (PRs) or better after the first two chemoimmunotherapy cycles occurred in 42 of 63 evaluable patients (66.7%; 95% CI, 55.0 to 78.3). Primary tumor volume decreased by a median of 75% (range, 100% [complete disappearance]-5% growth). Median peak hu14.18K322A serum levels in cycle one correlated with early response to therapy ( P = .0154, one-sided t-test). Sixty of 62 patients (97%) had an end-of-induction partial response or better. No patients experienced progressive disease during induction. The 3-year EFS was 73.7% (95% CI, 60.0 to 83.4), and the OS was 86.0% (95% CI, 73.8 to 92.8), respectively. CONCLUSION Adding hu14.18K322A to induction chemotherapy improved early objective responses, significantly reduced tumor volumes in most patients, improved end-of-induction response rates, and yielded an encouraging 3-year EFS. These results, if validated in a larger study, may be practice changing.

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Section: Discussionmentioning

confidence: 99%

Improved Outcome in Children With Newly Diagnosed High-Risk Neuroblastoma Treated With Chemoimmunotherapy: Updated Results of a Phase II Study Using hu14.18K322A

Furman

McCarville

Shulkin

et al. 2022

JCO

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“…Both the value‐adding ability and invasive activity of GD2‐transfected cells were significantly enhanced, and cell growth was significantly inhibited by the addition of monoclonal antibody 99 . Mujoo et al and Mueller et al demonstrated that mouse anti‐GD2 monoclonal antibodies 14.G2a and ch14.18 have a high affinity for GD2‐positive neuroblastoma cells and can effectively direct the antibody‐dependent cell‐mediated cytotoxicity 104,105 . The data suggest that the monoclonal antibody 14.18 binds strongly to SCLC cell lines and mediates tumor burn killing both in vivo and in vitro 106 .…”

Section: Disialogangliosidementioning

confidence: 99%

Advances in new targets for immunotherapy of small cell lung cancer

Zheng,

Liu,

et al. 2023

Thoracic Cancer

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Small cell lung cancer (SCLC) is one of the highly aggressive malignancies characterized by rapid growth and early metastasis, but treatment options are limited. For SCLC, carboplatin or cisplatin in combination with etoposide chemotherapy has been considered the only standard of care, but the standard first‐line treatment only results in 10‐month survival. The majority of patients relapse within a few weeks to months after treatment, despite the relatively sensitive response to chemotherapy. Over the past decade, immunotherapy has made significant progress in the treatment of SCLC patients. However, there have been limited improvements in survival rates for SCLC patients with the current immune checkpoint inhibitors PD‐1/PD‐L1 and CTLA‐4. In the face of high recurrence rates, small beneficiary populations, and low survival benefits, the exploration of new targets for key molecules and signals in SCLC and the development of drugs with novel mechanisms may provide fresh hope for immunotherapy in SCLC. Therefore, the aim of this review was to explore four new targets, DLL3, TIGIT, LAG‐3, and GD2, which may play a role in the immunotherapy of SCLC to find useful clues and strategies to improve the outcome for SCLC patients.

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“…We first validated that GD2 expression could be observed and quantified on neuroblastoma patient-derived cell lines (PDCLs) using dinutuximab directly conjugated to Alexa Fluor 647. The specificity of ch14.18 (dinutuximab) for GD2 has been previously validated [44][45][46]. We characterized dinutuximab binding across a panel of ten patientderived neuroblastoma PDCLs that represented a variety of disease stages and tumor types.…”

Section: Evaluation Of Surface Markers On Neuroblastoma Cell Linesmentioning

confidence: 99%

A Multi-Color Flow Cytometric Assay for Quantifying Dinutuximab Binding to Neuroblastoma Cells in Tumor, Bone Marrow, and Blood

Keyel,

Furr,

Kang

et al. 2023

JCM

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GD2, a disialoganglioside, is present on the surface of most neuroblastomas, as well as on some other cancers, such as melanoma and osteogenic sarcoma. The anti-GD2 antibody ch14.18 (dinutuximab) has an FDA-registered indication for use as maintenance therapy for high-risk neuroblastoma with cytokines and 13-cis-retinoic acid after myeloablative therapy. Recent studies using immunohistochemistry of tumor or tumor cells in marrow have shown that some neuroblastomas are negative for GD2. Dinutuximab and other anti-GD2 antibodies are increasingly used in combination with cytotoxic chemotherapy for treating relapsed neuroblastoma, so it is important to be able to identify patients with tumor cells with low GD2 expression, as such patients may experience toxicity but not benefit from the antibody therapy. As the most common clinical samples available for relapsed neuroblastoma are bone marrow aspirates, we developed a method to quantify dinutuximab binding density and the frequency of neuroblastoma cells positive for the antibody in bone marrow aspirates. Here, we describe a multi-color flow cytometry assay that employs non-GD2 antibodies to identify neuroblastoma cells in a mixed population (tumor, bone marrow, or blood) and an anti-GD2 antibody to quantify both the frequency and density of GD2 expression on neuroblastoma cells.

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Enhancement of antibody-dependent cytotoxicity with a chimeric anti-GD2 antibody.

Cited by 159 publications

References 0 publications

Improved Outcome in Children With Newly Diagnosed High-Risk Neuroblastoma Treated With Chemoimmunotherapy: Updated Results of a Phase II Study Using hu14.18K322A

Improved Outcome in Children With Newly Diagnosed High-Risk Neuroblastoma Treated With Chemoimmunotherapy: Updated Results of a Phase II Study Using hu14.18K322A

Advances in new targets for immunotherapy of small cell lung cancer

A Multi-Color Flow Cytometric Assay for Quantifying Dinutuximab Binding to Neuroblastoma Cells in Tumor, Bone Marrow, and Blood

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