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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2003-9-25
pubmed:abstractText
Previously using a series of monovalent vaccines, we demonstrated that the optimal method for inducing an antibody response against cancer cell-surface antigens is covalent conjugation of the antigens to keyhole limpet hemocyanin (KLH) and the use of a saponin adjuvant. We have prepared a heptavalent-KLH conjugate vaccine containing the seven epithelial cancer antigens GM2, Globo H, Lewis(y), TF(c), Tn(c), STn(c), and glycosylated MUC1. In preparation for testing this vaccine in the clinic, we tested the impact on antibody induction of administering the individual conjugates plus adjuvant compared with a mixture of the seven conjugates plus adjuvant, and of several variables thought to augment immunogenicity. These include approaches for decreasing suppressor cell activity or increasing helper T-lymphocyte activity (low dose cyclophosphamide or anti-CTLA-4 MAb), different saponin adjuvants at various doses (QS-21 and GPI-0100), and different methods of formulation (lyophilization and use of polysorbate 80). We find that: (1). Immunization with the heptavalent-KLH conjugate plus GPI-0100 vaccine induces antibodies against the seven antigens of comparable titer to those induced by the individual-KLH conjugate vaccines, high titers of antibodies against Tn (median ELISA titer IgM/IgG 320/10240), STn (640/5120), TF (320/10240), MUC1 (80/20480), and globo H (640/40); while lower titers of antibodies against Lewis(y)()(160/0) and only occasional antibodies against GM2 are induced. (2). These antibodies reacted with the purified synthetic antigens by ELISA, and with naturally expressed antigens on the cancer cell surface by FACS. (3). None of the approaches for further altering the suppressor cell/helper T-cell balance nor changes to the standard formulation by lyophilization or use of polysorbate 80 had any impact on antibody titers. (4). An optimal dose of saponin adjuvant, QS-21 (50 microg) or GPI-0100 (1000 microg), is required for optimal antibody titers. This heptavalent vaccine is sufficiently optimized for testing in the clinic.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Neoplasm, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Neoplasm, http://linkedlifedata.com/resource/pubmed/chemical/Cancer Vaccines, http://linkedlifedata.com/resource/pubmed/chemical/Gangliosides, http://linkedlifedata.com/resource/pubmed/chemical/Hemocyanin, http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin G, http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin M, http://linkedlifedata.com/resource/pubmed/chemical/Lewis Blood-Group System, http://linkedlifedata.com/resource/pubmed/chemical/Lewis Y antigen, http://linkedlifedata.com/resource/pubmed/chemical/MUC1 tandem repeat peptide, http://linkedlifedata.com/resource/pubmed/chemical/Mucin-1, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments, http://linkedlifedata.com/resource/pubmed/chemical/QS 21, http://linkedlifedata.com/resource/pubmed/chemical/Saponins, http://linkedlifedata.com/resource/pubmed/chemical/Vaccines, Conjugate, http://linkedlifedata.com/resource/pubmed/chemical/keyhole-limpet hemocyanin
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0340-7004
pubmed:author
pubmed:issnType
Print
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
608-16
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:12811527-Animals, pubmed-meshheading:12811527-Antibodies, Neoplasm, pubmed-meshheading:12811527-Antibody Formation, pubmed-meshheading:12811527-Antigens, Neoplasm, pubmed-meshheading:12811527-Cancer Vaccines, pubmed-meshheading:12811527-Drug Evaluation, Preclinical, pubmed-meshheading:12811527-Female, pubmed-meshheading:12811527-Gangliosides, pubmed-meshheading:12811527-Hemocyanin, pubmed-meshheading:12811527-Immunization, pubmed-meshheading:12811527-Immunoglobulin G, pubmed-meshheading:12811527-Immunoglobulin M, pubmed-meshheading:12811527-Lewis Blood-Group System, pubmed-meshheading:12811527-Mice, pubmed-meshheading:12811527-Mice, Inbred BALB C, pubmed-meshheading:12811527-Mice, Inbred C57BL, pubmed-meshheading:12811527-Mucin-1, pubmed-meshheading:12811527-Neoplasms, Glandular and Epithelial, pubmed-meshheading:12811527-Peptide Fragments, pubmed-meshheading:12811527-Saponins, pubmed-meshheading:12811527-T-Lymphocytes, pubmed-meshheading:12811527-Vaccination, pubmed-meshheading:12811527-Vaccines, Conjugate
pubmed:year
2003
pubmed:articleTitle
A preclinical study comparing approaches for augmenting the immunogenicity of a heptavalent KLH-conjugate vaccine against epithelial cancers.
pubmed:affiliation
Laboratory of Tumor Vaccinology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. ragupatg@mskcc.org
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't