Immunization of melanoma patients with BEC2-keyhole limpet hemocyanin plus BCG intradermally followed by intravenous booster immunizations with BEC2 to induce anti-GD3 ganglioside antibodies Journal Article

  

Authors:	Yao, T. J.; Meyers, M.; Livingston, P. O.; Houghton, A. N.; Chapman, P. B.
Article Title:	Immunization of melanoma patients with BEC2-keyhole limpet hemocyanin plus BCG intradermally followed by intravenous booster immunizations with BEC2 to induce anti-GD3 ganglioside antibodies
Abstract:	BEC2 is an anti-idiotypic mouse monoclonal antibody that mimics GD3 ganglioside. Previous clinical trials demonstrated that intradermal immunization using 2.5 mg of BEC2 with BCG or i.v. immunization with 10 mg of BEC2 can induce anti-GD3 antibodies in a subset of patients. We hypothesized that combining these two immunization strategies might be more effective in inducing anti-GD3 antibodies and that conjugation of BEC2 to keyhole limpet hemocyanin (KLH) would further enhance the immunogenicity of BEC2. In this clinical trial, 18 melanoma patients who were free of disease after complete surgical resection within 1-6 months received intradermal immunizations on weeks 0, 2, 4, 6, and 10 with 2.5 mg of BEC2 conjugated to KLH and mixed with BCG (BEC2-KLH/BCG). Booster immunizations of 10 mg of unconjugated BEC2 were administered i.v. on weeks 24, 37, and 50. Four of 18 patients (22%) developed IgM anti-GD3 antibodies. No IgG anti-GD3 antibodies were detected. All four responding patients developed anti-GD3 IgM during immunization with BEC2-KLH/BCG; only one patient demonstrated a reboost of the IgM anti-GD3 titer during the i.v. immunizations. Thirteen of the patients are free of melanoma (3 after undergoing re-resection for local relapse); 14 patients (78%) remain alive with a median follow-up of 28 months. These results confirm our previous trial, showing that BEC2 with BCG can induce anti-GD3 antibodies in patients. The data do not provide evidence that conjugation to KLH increases the immunogenicity of BEC2 when it is administered with BCG.
Keywords:	adult; clinical article; aged; middle aged; cancer surgery; unclassified drug; clinical trial; animals; mice; bcg vaccine; melanoma; drug administration schedule; monoclonal antibody; cancer regression; antibodies, monoclonal; cancer vaccines; immunogenicity; cancer immunization; injections, intradermal; adjuvants, immunologic; infusions, intravenous; antibodies, neoplasm; immunoglobulin g antibody; ganglioside gd3; antibody production; intravenous drug administration; drug formulation; keyhole limpet hemocyanin; immunoglobulin m antibody; hemocyanin; intradermal drug administration; immunization, secondary; conjugation; gangliosides; antibody conjugate; immunoconjugates; ganglioside antibody; monoclonal antibody bec2; antiidiotypic antibody; humans; human; male; female; priority journal; article; theracys
Journal Title:	Clinical Cancer Research
Volume:	5
Issue:	1
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Date Published:	1999-01-01
Start Page:	77
End Page:	81
Language:	English
PUBMED:	9918205
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0032943590&partnerID=40&md5=215e9f18df0bf0d555ca77bbb8828fd5
Notes:	Article -- Export Date: 16 August 2016 -- Source: Scopus

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