NDLI: Serological response patterns of melanoma patients immunized with a GM2 ganglioside conjugate vaccine.

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Serological response patterns of melanoma patients immunized with a GM2 ganglioside conjugate vaccine.

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Serological response patterns of melanoma patients immunized with a GM2 ganglioside conjugate vaccine.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kitamura, K. Stockert, E. Ritter, G. Old, L. J. Livingston, P. O. Helling, F. Oettgen, H. F. Fortunato, S. R.
Description	Author Affiliation: Kitamura K ( Ludwig Institute for Cancer Research, New York Unit, NY, USA.);
Abstract	Gangliosides, such as GM2, GD2, GD3, and 9-O-acetyl GD3, are receiving attention as targets for antibody-based and vaccine-based therapies of melanoma. GM2 appears to be a particularly immunogenic ganglioside in humans, as indicated by the presence of naturally occurring IgM anti-GM2 antibodies in approximately 5% of humans and the fact that immunization with irradiated GM2-expressing melanoma cells or purified GM2 adherent to bacillus Calmette-Guérin elicits GM2 antibodies of low to moderate titers in a high proportion of vaccinated patients. To develop vaccines that consistently induce high titers of IgM as well as IgG anti-GM2 antibodies, vaccines containing GM2 conjugated to keyhole limpet hemocyanin as the carrier protein and QS-21 as the adjuvant have been constructed. The serological response of vaccinated patients was monitored by ELISA using purified GM2 ganglioside for IgM and IgG anti-GM2 antibodies and for GM2 cell surface-reactive antibodies by immune adherence assays and cytotoxic tests (IgM antibodies) and mixed hemadsorption assays (IgG antibodies). The majority of vaccinated patients developed IgM and IgG antibodies detectable by ELISA. In most cases, the results of IgM ELISA correlated with assays for cell surface-reactive IgM antibodies. This was not true for IgG anti-GM2 antibodies, where strong discrepancies were seen between high titers in ELISA and little or no reactivity in mixed hemadsorption tests for cell surface-reactive antibodies. These IgG antibodies (and the less frequent IgM antibodies that show similar discrepancies) may be directed against GM2 determinants that are buried, hidden, or not present on GM2-expressing target cells. With regard to a major objective of ganglioside vaccines--i.e., generation of cytotoxic antibodies--the GM2-keyhole limpet hemocyanin/QS-21 vaccine is clearly superior to the previously tested GM2/bacillus Calmette-Guérin vaccine. However, variability in patient response and lack of persistence of high-titered IgM cytotoxic antibodies in many patients are problems that remain to be solved.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	7
Volume Number	92
Language	English
Publisher	National Academy of Sciences
Publisher Date	1995-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	G(M2) Ganglioside Immunology Melanoma Therapy Vaccines, Synthetic Therapeutic Use Adjuvants, Immunologic Animals Brain Metabolism Cyclophosphamide Enzyme-Linked Immunosorbent Assay Isolation & Purification Hemocyanin Immunoglobulin G Blood Immunoglobulin M Monitoring, Immunologic Neoplasm Staging Tay-Sachs Disease Time Factors Comparative Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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