Immunization of melanoma patients with antiidiotypic monoclonal antibody BEC2 (which mimics GD3 ganglioside): Pilot trials using no immunological adjuvant Journal Article

  


Authors: Chapman, P. B.; Livingston, P. O.; Morrison, M. E.; Williams, L.; Houghton, A. N.
Article Title: Immunization of melanoma patients with antiidiotypic monoclonal antibody BEC2 (which mimics GD3 ganglioside): Pilot trials using no immunological adjuvant
Abstract: GD3 ganglioside is an appealing target for immunotherapy of melanoma but attempts to induce active immunity against GD3 have been unsuccessful. We have begun to explore an alternative strategy using a murine antiidiotypic monoclonal antibody (MAb), designated BEC2, that mimics GD3. Twenty-one patients with AJCC stage IV melanoma were immunized with 2.5 mg of BEC2 administered subcutaneously on weeks 0, 2, 4, 6, and 10. Six patients had been treated previously with R24, a murine anti-GD3 MAb against which BEC2 was raised, permitting the evaluation of Ab2 immunization in patients previously exposed to Ab1. Eleven of 20 (55%) evaluable patients developed IgG against BEC2; 1 of these patients developed antibodies against GD3. No serious adverse effects were observed and no major tumor responses occurred. Two of six patients previously treated with R24 did not develop antibodies against either R24 or BEC2, suggesting they were unable to respond immunologically to murine immunoglobulin. Previous exposure to R24 did not prime patients to respond to BEC2 although BEC2 administration induced anti-BEC2 antibodies in these patients against epitopes not expressed by R24. We conclude that BEC2 administration is safe at the dose and schedule used, even in patients previously exposed to murine MAb. Although the immunogenicity of BEC2, as gauged by the anti-BEC2 antibody response, was low, one patient developed anti-GD3 antibodies. This is the first clinical experience using an antiidiotypic MAb that mimics a nonprotein antigen and the first use of an Ab2 in patients previously treated with Ab1. Future trials will build on these findings to augment the immunogenicity of BEC2.
Keywords: adult; clinical article; aged; unclassified drug; clinical trial; fatigue; cisplatin; fluorouracil; diarrhea; disease classification; drug safety; alpha interferon; carboplatin; dacarbazine; melanoma; nausea; thrombocytopenia; carmustine; chlormethine; ifosfamide; monoclonal antibody; fever; pruritus; rash; thorax pain; immune response; immunotherapy; immunoglobulin g; immunogenicity; antibody response; tamoxifen; immunological adjuvant; hyperbilirubinemia; headache; antibody; ganglioside gd3; intravenous drug administration; colony stimulating factor 1; recombinant interleukin 2; pleurisy; tumor necrosis factor; immunization; central nervous system disease; levamisole; active immunization; idiotypic antibody; rhinorrhea; subcutaneous drug administration; human; male; female; priority journal; article; monoclonal antibody bec 2; zeniplatin
Journal Title: Vaccine Research
Volume: 3
Issue: 2
ISSN: 1056-7909
Publisher: Mary Ann Liebert, Inc.  
Date Published: 1994-01-01
Start Page: 59
End Page: 69
Language: English
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0028048757&partnerID=40&md5=2ac26cc7b6a2008a58edeecf366e8eec
Notes: VACCINE RES. -- Cited By :24 -- Export Date: 14 January 2019 -- Article -- CODEN: VAREE -- Source: Scopus