Generation and Characterization of a Human/Mouse Chimeric GD2-Mimicking Anti-Idiotype Antibody Ganglidiximab for Active Immunotherapy against Neuroblastoma

  title={Generation and Characterization of a Human/Mouse Chimeric GD2-Mimicking Anti-Idiotype Antibody Ganglidiximab for Active Immunotherapy against Neuroblastoma},
  author={Christin Eger and Nikolai Siebert and Diana Seidel and Maxi Zumpe and Madlen J{\"u}ttner and Sven Brandt and H P M{\"u}ller and Holger N Lode},
  journal={PLoS ONE},
Vaccination with proteins mimicking GD2 that is highly expressed on neuroblastoma (NB) cells is a promising strategy in treatment of NB, a pediatric malignancy with poor prognosis. We previously showed efficacy of ganglidiomab in vivo, a murine anti-idiotype (anti-Id) IgG1. In order to tailor immune responses to variable regions, we generated a new human/mouse chimeric anti-Id antibody (Ab) ganglidiximab by replacing murine constant fragments with corresponding human IgG1 regions. DNA sequences… 
Structural Mimicry of the Dengue Virus Envelope Glycoprotein Revealed by the Crystallographic Study of an Idiotype–Anti-idiotype Fab Complex
The utility of employing an anti-idiotype antibody to monitor a patient's specific immune responses is demonstrated and routes for the improvement of E “mimicry” by E1 by increasing its recognition of the Fab HM14c10 light chain CDRs are suggested.
Screening and activity identification of an anti-idiotype nanobody for Bt Cry1F toxin from the camelid naive antibody phage display library
The anti-idiotypic nanobody 5B expressed through the prokaryotic system has the same activity as in phage form, and mortality compared to controls could reach 23.3% (P < 0.05).
Reformation in chimeric antigen receptor based cancer immunotherapy: Redirecting natural killer cell.
  • Chu Lin, J. Zhang
  • Medicine
    Biochimica et biophysica acta. Reviews on cancer
  • 2018
Although CAR-NK is considered as one of the most possible "off-the-shelf" products, the improvement for the efficiency of expansion and transduction as well as the solution for underlying safety issues is still needed.
Advances in Anti-GD2 Immunotherapy for Treatment of High-risk Neuroblastoma
A brief history of anti-GD2-based immunotherapy, current areas of neuroblastoma research targetingGD2, and potential diagnostic and therapeutic uses targeting GD2 are reviewed.
Cancer Vaccines in Pediatrics
This chapter focuses on the current status of pediatric cancer vaccines with an emphasis on current and completed clinical trials, and on approaches that might inform future directions in their use.
Cell death-based treatment of neuroblastoma
A thorough overview of how different modes of cell death and treatment strategies, such as immunotherapy or spontaneous regression, are or can be applied for NB elimination is provided.
Evolving treatments in high-risk neuroblastoma
This review highlights limitations in the treatment procedure and future therapies in development that may be adopted into clinical practice, compiled from a literature search of scientific papers from the last 30 years including ongoing clinical trials.
Neuroblastoma (Peripheral neuroblastic tumours).
In children with localised operable disease, surgical resection alone is usually a sufficient treatment, with 3-year event-free survival (EFS) being greater than 85% and primary chemotherapy followed by surgery and/or radiotherapy yields an EFS of around 75%.


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.
Induction of cellular immunity by anti-idiotypic antibodies mimicking GD2 ganglioside
The studies demonstrate the induction of ganglioside-specific T cell-dependent immunity by Ab2 in mice, and T cells showed specific reactivity to gangliosiside expressed by tumor cells.
Functional properties and effect on growth suppression of human neuroblastoma tumors by isotype switch variants of monoclonal antiganglioside GD2 antibody 14.18.
These studies suggest that a mechanism(s) other than Fc-directed complement-dependent cytotoxicity or antibody-dependent cell-mediated cytotoxic effects may account for the in vivo antitumor effects of these particular antibodies.
Serum half-life and tumor localization of a chimeric antibody deleted of the CH2 domain and directed against the disialoganglioside GD2.
A chimeric human/mouse antibody to the tumor-associated antigen ganglioside GD2 is engineered, with the aim of decreasing its serum half-life, maintaining its full antigen-binding capacity, and deleting its effector functions, thus making it a potentially useful reagent for the radioimaging of tumors.
Induction of IgG antibodies by an anti-idiotype antibody mimicking disialoganglioside GD2.
Results suggest that the anti-Id 1A7 can induce GD2-specific IgG antibodies that can recognize cell surface-associated as well as soluble disialoganglioside GD2.
Antibody-targeted interleukin 2 stimulates T-cell killing of autologous tumor cells.
The ability of resting 660 TIL cells to kill their autologous GD2-positive target cells was enhanced if the target cells were first coated with the fusion protein, and stimulation of killing was greater than that of uncoated cells in the presence of equivalent or higher concentrations of free IL2.
NK cells engineered to express a GD2-specific antigen receptor display built-in ADCC-like activity against tumour cells of neuroectodermal origin
Clonal derivatives of the clinically applicable human NK cell line NK‐92 are generated that stably express a GD2‐specific chimeric antigen receptor (CAR) comprising an anti‐GD2 ch14.18 single chain Fv antibody fusion protein with CD3‐ζ chain as a signalling moiety to combine specific antibody‐mediated recognition of NB cells with the potent cytotoxic activity of NK cells.
Anti-idiotype antibody vaccine therapy for cancer
The greatest challenge of immunotherapy by means of anti- Id vaccines is to identify the optimal anti-Id antibody that will function as a true surrogate antigen for a TAA system, and ideally will generate both humoral and cellular immune responses.
Disialoganglioside-specific human natural killer cells are effective against drug-resistant neuroblastoma
The data suggest that recognition of GD2 by the chimeric receptor is the primary mechanism involved in NK-92-scFv(ch14.18)-zeta-mediated lysis and is independent of activating NK cell receptor/ligand interactions.
Detection of ganglioside GD2 in tumor tissues and sera of neuroblastoma patients.
The GD2 serum level of one neuroblastoma patient, when followed serially, was found to correlate with progression of disease, suggesting the potential usefulness of this assay for the diagnosis and monitoring of Neuroblastoma.