A polyvalent vaccine for high-risk prostate patients: "Are more antigens better?" Journal Article

Authors: Slovin, S. F.; Ragupathi, G.; Fernandez, C.; Diani, M.; Jefferson, M. P.; Wilton, A.; Kelly, W. K.; Morris, M.; Solit, D.; Clausen, H.; Livingston, P.; Scher, H. I.
Article Title: A polyvalent vaccine for high-risk prostate patients: "Are more antigens better?"
Abstract: We have shown the immunogenicity and safety of synthetic carbohydrate vaccines when conjugated to the carrier keyhole limpet hemocyanin (KLH) and given with the adjuvant, QS-21, in patients with biochemically relapsed prostate cancer. To determine whether immune response could be further enhanced with stimulation by multiple antigens, a hexavalent vaccine was prepared using previously determined doses and administered in a Phase II setting to 30 high-risk patients. The hexavalent vaccine included GM2, Globo H, Lewis y, glycosylated MUC-1-32mer and Tn and TF in a clustered formation, conjugated to KLH and mixed with QS-21. Eight vaccinations were administered over 13 months. All 30 patients had significant elevations in antibody titers to at least two of the six antigens; 22 patients had increased reactivity with FACS. These serologic responses were lower than that seen previously in patients treated with the respective monovalent vaccines. The reciprocal median combined IgM and IgG antibody titers with ELISA against MUC1, Tn, TF, globo H and GM2 for these 30 patients were 640, 80, 120, 40 and 0, compared to 1280, 640, 1280, 320 and 160 seen in patients receiving individual monovalent vaccines. This hexavalent vaccine of synthetic "self" antigens broke immunologic tolerance against two or more antigens in all 30 vaccinated patients, was safe, but antibody titers against several of the antigens were lower than those seen in individual monovalent trials. No impact on PSA slope was detected. We address the relevance of the multivalent approach for prostate cancer treatment. © 2007 Springer-Verlag.
Keywords: adult; clinical article; controlled study; aged; aged, 80 and over; disease-free survival; middle aged; unclassified drug; human cell; drug safety; cancer patient; flow cytometry; prostate specific antigen; cancer prevention; immunoreactivity; enzyme linked immunosorbent assay; high risk patient; time factors; fever; prostate cancer; prostate-specific antigen; prostatic neoplasms; immunological tolerance; immune response; antigen; immunotherapy; antigens, neoplasm; immunoglobulin g; cancer vaccine; immunogenicity; cancer immunization; western blotting; psa; cancer relapse; injection site pain; immunological adjuvant; flu like syndrome; antibodies; cell strain mcf 7; fluorescence activated cell sorting; injection site erythema; immunoglobulin g antibody; vaccine; tn antigen; antibody titer; complement dependent cytotoxicity; keyhole limpet hemocyanin; immunoglobulin m antibody; hemocyanin; immunoglobulin m; globo h antigen; gm2 antigen; qs 21; tf antigen; injection site pruritus; injection site induration; polyvalent; carbohydrate vaccine; le antigen; muc 1 32mer antigen
Journal Title: Cancer Immunology, Immunotherapy
Volume: 56
Issue: 12
ISSN: 0340-7004
Publisher: Springer  
Date Published: 2007-12-01
Start Page: 1921
End Page: 1930
Language: English
DOI: 10.1007/s00262-007-0335-y
PUBMED: 17619878
PROVIDER: scopus
Notes: --- - "Cited By (since 1996): 20" - "Export Date: 17 November 2011" - "CODEN: CIIMD" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Andrew Wilton
    27 Wilton
  2. Susan Slovin
    186 Slovin
  3. Michael Morris
    280 Morris
  4. David Solit
    440 Solit
  5. Govindaswami Ragupathi
    133 Ragupathi
  6. Howard Scher
    834 Scher
  7. Meghan Diani
    5 Diani