Ganglioside conjugate vaccines: Immunotherapy against tumors of neuroectodermal origin Journal Article
| Authors: | Helling, F.; Livingston, P. O. |
| Article Title: | Ganglioside conjugate vaccines: Immunotherapy against tumors of neuroectodermal origin |
| Abstract: | Gangliosides are known to be suitable targets for immune attack against cancer but they are poorly immunogenic. Active immunization with ganglioside/BCG or liposome vaccines results in moderate titer IgM antibody responses of short duration. Covalent attachment of poorly immunogenic antigens to immunogenic proteins is a potent method for inducing an IgG antibody response. GD3, a dominant ganglioside on malignant melanoma, was modified by ozone cleavage of the double bond in the ceramide backbone, an aldehyde group introduced and used for coupling via reductive amination to ε-aminolysyl groups of proteins. Utilizing this method, GD3 conjugates were constructed with: 1. Synthetic multiple antigenic peptide (MAP) constructs expressing 4 repeats of a malaria T-cell epitope; 2. Outer membrane proteins (OMP) of Neisseria meningitidis; 3. Cationized bovine serum albumin; 4. Keyhole limpet hemocyanin (KLH); and 5. Polylysine. In addition, conjugates containing only the GD3 oligosaccharide were synthesized. All constructs were tested for antigenicity using anti-GD3 antibody R24, and for immunogenicity in mice. Serum antibody levels were analyzed by ELISA and immune thin-layer chromatography. Results in the mouse show a significant improvement in the IgM antibody response and a consistent IgG response against GD3 using GD3-KLH conjugates. Other carrier proteins and the use of GD3 oligosaccharide were significantly less effective. If improved immunogenicity and clinical benefit with conjugate vaccines can be demonstrated in patients with melanoma, this approach may be applicable to patients with other tumors of neuroectodermal origin, including gliomas, glioblastomas, astrocytomas, and neuroblastomas. © 1994 Humana Press Inc. |
| Keywords: | clinical trial; nonhuman; conference paper; mouse; animal; bcg vaccine; cancer immunotherapy; melanoma; animal model; cyclophosphamide; drug synthesis; immunotherapy; immunoglobulin g; cancer vaccines; immunogenicity; vaccination; vaccines, synthetic; polylysine; bovine serum albumin; vaccine production; tumor vaccine; double blind procedure; neuroectoderm tumor; neuroectodermal tumors; thin layer chromatography; immunoglobulin g antibody; drug conjugation; ganglioside gd3; ganglioside gm2; antibody formation; neuroblastomas; keyhole limpet hemocyanin; immunoglobulin m antibody; immunoglobulin m; astrocytomas; gangliosides; antibody blood level; glioblastomas; gliomas; outer membrane protein; neisseria meningitidis; antigenicity; melanomas; glycoconjugates; human; priority journal |
| Journal Title: | Molecular and Chemical Neuropathology |
| Volume: | 21 |
| Issue: | 2-3 |
| ISSN: | 1044-7393 |
| Publisher: | Humana Press Inc |
| Date Published: | 1994-02-01 |
| Start Page: | 299 |
| End Page: | 309 |
| Language: | English |
| DOI: | 10.1007/bf02815357 |
| PROVIDER: | scopus |
| PUBMED: | 8086040 |
| DOI/URL: | |
| Notes: | Export Date: 14 January 2019 -- Article -- CODEN: MCHNE C2 -- Source: Scopus |
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