Impact of immunological adjuvants and administration route on HAMA response after immunization with murine monoclonal antibody MELIMMUNE-1 in melanoma patients Journal Article

  


Authors: Livingston, P. O.; Adluri, S.; Zhang, S.; Chapman, P.; Raychaudhuri, S.; Merritt, J. A.
Article Title: Impact of immunological adjuvants and administration route on HAMA response after immunization with murine monoclonal antibody MELIMMUNE-1 in melanoma patients
Abstract: MELIMMUNE-1 is a murine antiidiotype antibody that mimics an epitope on the high-molecular-weight chondroitin sulfate proteoglycan (MPG) expressed on melanoma cells. We describe here the results of a series of clinical trials aimed at identifying the optimal immunological adjuvant (BCG, purified saponin fraction QS-21, L121 emulsion or SAFm) and the optimal route of immunization (subcutaneous versus intravenous) for augmenting the immune response against MELIMMUNE-1. Since none of these immunization approaches resulted in an immune response against MPG within the detection of our standard resetting and flow cytometry serological assays, an assay measuring anti-MELIMMUNE-1 antibody titers (referred to here as human antimouse antibody or HAMA) was used as a surrogate gauge of immunogenicity. At a MELIMMUNE-1 dose of 2 mg in the absence of immunological adjuvants, the subcutaneous and intravenous routes of immunization gave comparable low titers of IgM and IgG HAMA responses (median 1/80). The immunological adjuvants L121 emulsion, SAFm, and QS-21 significantly increased IgM and IgG responses both with regard to the antibody titers obtained and the rapidity of the antibody response. The serologic response in the QS-21 group of patients was the strongest; the median IgM HAMA titer was 1/1280 while the median IgG response was 1/5120, both significantly higher than the immune response with no adjuvant. Our results demonstrate that the intravenous and subcutaneous routes of immunization result in comparable antibody titers but that the use of potent immunological adjuvants such as QS-21, L121 emulsion, and SAFm can greatly augment the serologic response against antiidiotype antibodies administered subcutaneously.
Keywords: clinical article; controlled study; human cell; clinical trial; flow cytometry; melanoma; controlled clinical trial; monoclonal antibody; arthralgia; fever; immune response; immunoglobulin g; immunogenicity; erythema; immunological adjuvant; immunoassay; tumor vaccine; serology; intravenous drug administration; skin ulcer; antibody titer; immunoglobulin m; immunization; saponin; idiotypic antibody; proteochondroitin sulfate; subcutaneous drug administration; human; priority journal; article
Journal Title: Vaccine Research
Volume: 4
Issue: 2
ISSN: 1056-7909
Publisher: Mary Ann Liebert, Inc.  
Date Published: 1995-01-01
Start Page: 87
End Page: 94
Language: English
PROVIDER: scopus
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-0029084194&partnerID=40&md5=9c8d9e53b2484cb417bd93b403873543
Notes: Article -- Export Date: 28 August 2018 -- Source: Scopus