PD-1 blockade augments anti-neuroblastoma immune response induced by anti-GD2 antibody ch14.18/CHO

@article{Siebert2017PD1BA,
  title={PD-1 blockade augments anti-neuroblastoma immune response induced by anti-GD2 antibody ch14.18/CHO},
  author={Nikolai Siebert and Maxi Zumpe and Madlen J{\"u}ttner and Sascha Troschke-Meurer and Holger N Lode},
  journal={OncoImmunology},
  year={2017},
  volume={6}
}
ABSTRACT Immunotherapy with anti-GD2 antibody (Ab) ch14.18/CHO is effective for treatment of high-risk neuroblastoma (NB) patients and is mainly based on GD2-specific Ab-dependent cellular cytotoxicity (ADCC). Strategies to further enhance the efficacy are important and currently explored in prospective clinical trials randomizing ch14.18/CHO ± IL-2. Recently, expression of programmed death 1 (PD-1) inhibitory receptor by effector cells and its ligand (PD-L1) by tumor cells has been shown. Here… 
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References

SHOWING 1-10 OF 30 REFERENCES
Anti-neuroblastoma effect of ch14.18 antibody produced in CHO cells is mediated by NK-cells in mice.
Immune activation and clinical responses following long-term infusion of anti-GD2 antibody ch14.18/CHO in combination with interleukin-2 in high-risk neuroblastoma patients.
TLDR
A less toxic treatment using long-term infusion of anti-GD2antibody ch14.18/CHO and subcutaneous interleukin-2 (IL-2) may improve outcome in high risk neuroblastoma (NB).
PD-L1 expression in metastatic neuroblastoma as an additional mechanism for limiting immune surveillance
TLDR
The data show that a PD-L1-mediated immune resistance mechanism occurs in metastatic neuroblasts and provide a biological rationale for blocking the PD-1/PD-Ls axis in future combined immunotherapeutic approaches.
TLR3 triggering regulates PD-L1 (CD274) expression in human neuroblastoma cells.
Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma.
TLDR
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.
Increasing the Clinical Efficacy of NK and Antibody-Mediated Cancer Immunotherapy: Potential Predictors of Successful Clinical Outcome Based on Observations in High-Risk Neuroblastoma
Disease recurrence is frequent in high-risk neuroblastoma (NBL) patients even after multi-modality aggressive treatment [a combination of chemotherapy, surgical resection, local radiation therapy,…
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…
Disialoganglioside-specific human natural killer cells are effective against drug-resistant neuroblastoma
TLDR
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.
Abstract CT410: Immune activation, clinical response and survival following long-term infusion of anti-GD2 antibody ch14.18/CHO in combination with interleukin-2 in high-risk neuroblastoma patients
TLDR
Continuous infusion of anti-GD2 Ab ch14.18/CHO reduces the pain side effect, shows clinical activity in NB patients and improves the outcome, and determination of antibody levels and functional immune parameters indicate persistent anti-neuroblastoma immune-activity measurable before susequent treatment cycles is indicated.
PD-L1 and CD8+PD1+ lymphocytes exist as targets in the pediatric tumor microenvironment for immunomodulatory therapy
TLDR
The presence of an active PD-L1 pathway in a high proportion of pediatric cancers is revealed, as demonstrated by strong PD- L1 positivity and the presence of PD-1 expressing CD8+ TILs.
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