Validated detection of human anti-chimeric immune responses in serum of neuroblastoma patients treated with ch14.18/CHO.

  title={Validated detection of human anti-chimeric immune responses in serum of neuroblastoma patients treated with ch14.18/CHO.},
  author={Nikolai Siebert and Christin Eger and Diana Seidel and Madlen J{\"u}ttner and Holger N Lode},
  journal={Journal of immunological methods},
Human/mouse chimeric monoclonal antibody (mAb) ch14.18/CHO is directed against disialoganglioside GD2. Activity and efficacy of this mAb are currently determined in ongoing clinical Phase II and -III studies in high-risk neuroblastoma (NB). Based on the chimeric nature of this mAb, some patients may develop a human anti-chimeric immune response (Mirick et al., 2004) which impacts on pharmacokinetics and may induce anti-anti-idiotype (Id) mAb with a potential survival benefit. Therefore, a… 
Functional Bioassays for Immune Monitoring of High-Risk Neuroblastoma Patients Treated with ch14.18/CHO Anti-GD2 Antibody
Effective treatment of high-risk neuroblastoma (NB) remains a major challenge in pediatric oncology. Human/mouse chimeric monoclonal anti-GD2 antibody (mAb) ch14.18 is emerging as a treatment option
Impact of HACA on Immunomodulation and Treatment Toxicity Following ch14.18/CHO Long-Term Infusion with Interleukin-2: Results from a SIOPEN Phase 2 Trial
GD2-directed immunotherapies improve survival of high-risk neuroblastoma (NB) patients (pts). Treatment with chimeric anti-GD2 antibodies (Ab), such as ch14.18, can induce development of human
Immunomonitoring of Stage IV Relapsed Neuroblastoma Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation and Subsequent GD2 (ch14.18/CHO) Antibody Treatment
In-patient functional immunomonitoring is shown to be feasible and valuable in contributing to the understanding of anti-cancer combinatorial treatments such as haplo SCT and antibody immunotherapy.
Spotlight on dinutuximab in the treatment of high-risk neuroblastoma: development and place in therapy
This review summarizes the development of GD2 antibody-targeted therapy, the use of dinutuximab in both up-front and salvage therapy for high-risk NB, and the potential mechanisms of resistance to dinutUXimab.
Differential killing of CD56-expressing cells by drug-conjugated human antibodies targeting membrane-distal and membrane-proximal non-overlapping epitopes
Antibody-drug conjugates made by conjugation with a highly potent pyrrolobenzodiazepine dimer exhibited killing activity that correlated with CD56 down-regulation, and to some extent with in vivo binding ability of the antibodies.
Pharmacokinetics and pharmacodynamics of ch14.18/CHO in relapsed/refractory high-risk neuroblastoma patients treated by long-term infusion in combination with IL-2
LTI of ch14.18/CHO induced effector mechanisms over the entire treatment period, and may therefore emerge as the preferred delivery method of anti-GD2 immunotherapy to NB patients.
The Promise of Anti-idiotype Revisited
The experience of polyclonal anti-Idiotype reagents in animal models as well as an understanding of the immune response in humans lends to the proposition thatpolyclonalanti-idiotype vaccines will be more effective compared to monoclonal-based anti- Idiotypevaccines.
Approaches to Passive and Active Vaccination against Neuroblastoma
Immunotherapy of neuroblastoma is emerging as an important treatment option to further improve outcome for patients suffering from this challenging pediatric malignancy. In this short overview, curren
Mechanism and efficacy of a GD2-specific immunotherapy using NK cells
D i s s e r t a t i o n zur Erlangung des akademischen Grades d o c t o r r e r u m n a t u r a l i u m


Validated detection of anti-GD2 antibody ch14.18/CHO in serum of neuroblastoma patients using anti-idiotype antibody ganglidiomab.
Human/mouse chimeric monoclonal antibody (mAb) ch14.18 is directed against disialoganglioside GD2 and has demonstrated activity and efficacy in high-risk neuroblastoma (NB). For the purpose of
Human antiglobulin response to foreign antibodies: therapeutic benefit?
HAGA should not a priori preclude the therapeutic use of Ab for cancer, and studies have shown that some patients have unexpectedly prolonged survival associated with HAGA.
Vaccination with anti-idiotype antibody ganglidiomab mediates a GD2-specific anti-neuroblastoma immune response
The induction of a GD2-specific immune response with ganglidiomab, a new anti-idiotype antibody to anti-GD2 antibodies of the 14.18 family is reported, proving GD2 surrogate function and anti-IDiotype characteristics and demonstrating activity against neuroblastoma.
Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma.
Immunotherapy with ch14.18, GM-CSF, and interleukin-2 was associated with a significantly improved outcome as compared with standard therapy in patients with high-risk neuroblastoma.
Consolidation treatment with chimeric anti-GD2-antibody ch14.18 in children older than 1 year with metastatic neuroblastoma.
  • T. Simon, B. Hero, +4 authors F. Berthold
  • Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2004
Consolidation treatment of stage 4 neuroblastoma with ch14.18 was associated with considerable but manageable side effects and Multivariate analysis failed to demonstrate an advantage of antibody treatment for EFS and OS.
A review of human anti-globulin antibody (HAGA, HAMA, HACA, HAHA) responses to monoclonal antibodies. Not four letter words.
  • G. Mirick, B. Bradt, S. Denardo, G. Denardo
  • Medicine
    The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of...
  • 2004
A survival advantage has been observed in some patients who developed a HAGA following treatment with MAbs, and correlates with development of an anti-idiotype antibody cascade directed toward the MAbs used to treat these patients.
Targeted Immunotherapy for High-Risk Neuroblastoma—The Role of Monoclonal Antibodies
Multiple GD2-specific monoclonal antibodies have been researched over the last decade in patients diagnosed with high-risk neuroblastoma, and one anti-GD2 antibody, ch14.18, was found to significantly improve event-free and overall survival of high- Risk Neuroblastoma.
Long term outcome of high-risk neuroblastoma patients after immunotherapy with antibody ch14.18 or oral metronomic chemotherapy
Follow-up analysis of the patient cohort indicated that immunotherapy with MAB ch14.18 may prevent late relapses and metronomic oral maintenance chemotherapy also appeared effective.
Recommendations for the Bioanalytical Method Validation of Ligand-Binding Assays to Support Pharmacokinetic Assessments of Macromolecules
Recommendations for the development, validation, and implementation of ligand binding assays (LBAs) that are intended to support pharmacokinetic and toxicokinetic assessments of macromolecules are made.
Confirmatory reanalysis of incurred bioanalytical samples
Recommendations concerning the number and types of samples that should be analyzed in such an evaluation, as well as the manner in which the resultant data should be analyze are provided.