Phase I trial of murine monoclonal antibody 14G2a administered by prolonged intravenous infusion in patients with neuroectodermal tumors.

Murray, James L.; Cunningham, Joan E.; Brewer, H. Winslow; Mujoo, Kalpana; Zukiwski, Alexander; Podoloff, Donald A.; Kasi, Leela P.; Bhadkamkar, Viju; Fritsche, H. A.; Benjamin, Robert S.

doi:10.1200/jco.1994.12.1.184

Cited by 114 publications

(60 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The hybridoma cell line secreting the mouse monoclonal antibody 14G2a was provided by Dr R. A. Reisfeld (The Scripps Institute, La Jolla, CA, USA). The antibody is of the IgG2a isotype, and binds to GD2 ganglioside (24). For all experiments, the antibody was purified from cell culture media using HI TRAP protein G columns according to the manufacturer's protocol (Amersham Biosciences AB, Uppsala, Sweden).…”

Section: Methodsmentioning

confidence: 99%

Selection of novel peptide mimics of the GD2 ganglioside from a constrained phage-displayed peptide library

Horwacik

Czaplicki²,

Talarek³

et al. 2007

Int J Mol Med

View full text Add to dashboard Cite

Abstract. Aberrant glycosylation is a universal feature of cancer cells. There are quantitative and qualitative changes in expression of gangliosides observed in tumors of a neuroectodermal origin such as neuroblastoma, melanoma and astrocytoma. The presence of large amounts of GD2 ganglioside on neuroblastoma cells, as compared to normal cells, opens the possibilities to use the tumor-associated carbohydrate antigen in diagnosis and immunotherapeutic approaches. In the quest for immunogens potentially capable of eliciting anti-GD2 ganglioside immune responses, we performed affinity purification of phage-displayed peptides from the LX-8 library (12-mer containing disulphide bridge). The library was screened with the biotinylated anti-GD2 ganglioside 14G2a mAb monoclonal antibody. Our goal was to isolate and characterize peptide mimics of GD2 ganglioside. Numerous individual phage clones that bound 14G2a mAb were identified with the application of immunoblotting technique in the phage pools yielded from the pannings. The phage-borne peptides were tested for their anti-GD2 ganglioside antibody binding ability using ELISA. Among these clones five different phage-displayed peptide sequences were identified. Moreover, we showed that the secondary structure of the peptides, stabilized by the disulfide bridging between cysteine residues at positions 2 and 11, was crucial for the binding of the peptides to 14G2a mAb. In a separate set of experiments, we observed a competition of the peptides, expressed on phages as well as in their synthetic form, with the nominal antigen GD2 ganglioside expressed on IMR-32 neuroblastoma cells for binding to 14G2a mAb. Based on the obtained results we concluded that all of these 5 peptides were mimics of the GD2 ganglioside.

show abstract

Section: Methodsmentioning

confidence: 99%

Selection of novel peptide mimics of the GD2 ganglioside from a constrained phage-displayed peptide library

Horwacik

Czaplicki²,

Talarek³

et al. 2007

Int J Mol Med

View full text Add to dashboard Cite

show abstract

“…Antibodies (Ab) against tumor-associated antigens can induce complement dependent cytotoxicity (CDC) and Ab-dependent cell-mediated cytotoxicity (ADCC) [70]. Promising pediatric clinical phase I trials have been described using monoclonal Ab against gangliosides, which are highly expressed in neuroblastoma and osteosarcoma [40,87,88,128]. Tumor-speciWc Ab [86,105].…”

Section: Antibodiesmentioning

confidence: 99%

Targets for active immunotherapy against pediatric solid tumors

Jacobs

Coulie

Figdor

et al. 2008

Cancer Immunol Immunother

View full text Add to dashboard Cite

The potential role of antibodies and T lymphocytes in the eradication of cancer has been demonstrated in numerous animal models and clinical trials. In the last decennia new strategies have been developed for the use of tumor-speciWc T cells and antibodies in cancer therapy. EVective anti-tumor immunotherapy requires the identiWcation of suitable target antigens. The expression of tumorspeciWc antigens has been extensively studied for most types of adult tumors. Pediatric patients should be excellent candidates for immunotherapy since their immune system is more potent and Xexible as compared to that of adults. So far, these patients do not beneWt enough from the progresses in cancer immunotherapy, and one of the reasons is the paucity of tumor-speciWc antigens identiWed on pediatric tumors. In this review we discuss the current status of cancer immunotherapy in children, focusing on the identiWcation of tumor-speciWc antigens on pediatric solid tumors.

show abstract

“…In addition, the Fc-fragment of the murine antibody may not elicit ADCC or CDC as effectively as the Fc portion of a human antibody, as described above [45,46,47,48,49].…”

Section: Gd2 and Anti-gd2 Antibody Immunotherapymentioning

confidence: 99%

Fenretinide sensitizes multidrug-resistant human neuroblastoma cells to antibody-independent and ch14.18-mediated NK cell cytotoxicity

et al. 2012

View full text Add to dashboard Cite

Phase I trial of murine monoclonal antibody 14G2a administered by prolonged intravenous infusion in patients with neuroectodermal tumors.

Abstract: Mab 14G2a has modest antitumor activity at the expense of significant toxicity. Dose-limiting neurologic sequelae may significantly limit phase II studies other than in pediatric patients with neuroblastoma.

Cited by 114 publications

References 12 publications

Selection of novel peptide mimics of the GD2 ganglioside from a constrained phage-displayed peptide library

Selection of novel peptide mimics of the GD2 ganglioside from a constrained phage-displayed peptide library

Targets for active immunotherapy against pediatric solid tumors

Fenretinide sensitizes multidrug-resistant human neuroblastoma cells to antibody-independent and ch14.18-mediated NK cell cytotoxicity

Contact Info

Product

Resources

About