Sequential immunization of melanoma patients with GD3 ganglioside vaccine and anti-idiotypic monoclonal antibody that mimics GD3 ganglioside Journal Article

Authors: Chapman, P. B.; Wu, D.; Ragupathi, G.; Lu, S.; Williams, L.; Hwu, W. J.; Johnson, D.; Livingston, P. O.
Article Title: Sequential immunization of melanoma patients with GD3 ganglioside vaccine and anti-idiotypic monoclonal antibody that mimics GD3 ganglioside
Abstract: GD3 ganglioside is an attractive target for immunotherapy of melanoma because it is abundantly expressed on all melanomas but not expressed on most normal tissues. Although GD3 has proven to be one of the least immunogenic gangliosides, our recent studies showed that anti-GD3 antibodies can be induced in patients immunized either with GD3-lactone-KLH (GD3-L-KLH) plus QS-21 adjuvant or with BEC2 anti-idiotypic monoclonal antibody vaccine, which mimics GD3, plus Bacillus Calmette-Guérin. We compared the immunogenicity of these two vaccines and tested whether one vaccine could prime an antibody response to the other. This is the first clinical trial immunizing patients with both antigen and anti-idiotypic monoclonal antibody vaccine. Twenty-four melanoma patients were randomized to be immunized with either BEC2 followed by GD3-L-KLH or in the opposite order. Our prior study suggested that a 25-μg dose of BEC2 was more immunogenic than our standard dose of 2.5 mg and therefor was used in this trial. Overall, 10 of 24 patients (42%) developed anti-GD3 antibodies detectable by ELISA, five in each cohort. All antibody responses were in response to the GD3-L-KLH vaccine. We found no evidence of priming by either vaccine. Antibody responses did not correlate with survival outcomes. Cellular responses were detected by enzyme-linked immunospot against BEC2, Bacillus Calmette-Guérin, and KLH, but not against GD3. We confirmed that GD3-L-KLH vaccine induces anti-GD3 antibodies, but we were unable to confirm our previous finding that a 25-μg dose of BEC2 is immunogenic. Future multivalent ganglioside vaccines should include the GD3-L-KLH vaccine.
Keywords: adolescent; adult; cancer survival; clinical article; controlled study; treatment outcome; middle aged; unclassified drug; clinical trial; neoplasm staging; t-lymphocytes; bcg vaccine; cancer immunotherapy; melanoma; controlled clinical trial; randomized controlled trial; enzyme linked immunosorbent assay; monoclonal antibody; immune response; immunoglobulin g; cancer vaccines; immunogenicity; antibody response; enzyme-linked immunosorbent assay; ganglioside gd3; vaccine; antibody titer; vaccines, conjugate; immunization; qs 21; gangliosides; antibodies, anti-idiotypic; lactone; antiidiotypic antibody; humans; human; male; female; priority journal; article; bec2 vaccine; ganglioside gd3 lactone klh vaccine
Journal Title: Clinical Cancer Research
Volume: 10
Issue: 14
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2004-07-15
Start Page: 4717
End Page: 4723
Language: English
DOI: 10.1158/1078-0432.ccr-04-0345
PROVIDER: scopus
PUBMED: 15269144
Notes: Clin. Cancer Res. -- Cited By (since 1996):44 -- Export Date: 16 June 2014 -- CODEN: CCREF -- Source: Scopus
Altmetric Score
MSK Authors
  1. Yue Wu
    8 Wu
  2. Wen-Jen Hwu
    28 Hwu
  3. Govindaswami Ragupathi
    134 Ragupathi
  4. Paul Chapman
    260 Chapman
  5. Xing-Gu Lu
    5 Lu