Impact of minimal tumor burden on antibody response to vaccination Journal Article


Authors: Kim, S. K.; Wu, X.; Ragupathi, G.; Gathuru, J.; Koide, F.; Cheung, N. K.; Panageas, K.; Livingston, P. O.
Article Title: Impact of minimal tumor burden on antibody response to vaccination
Abstract: Four randomized phase III trials conducted recently in melanoma patients in the adjuvant setting have been based in part on the correlation between antibody responses in immunized patients and improved survival. Each of these randomized trials demonstrated no clinical benefit, although again there was a significant correlation between antibody response after vaccination and disease free and overall survival. To better understand this paradox, we established a surgical adjuvant model targeting GD2 ganglioside on EL4 lymphoma cells injected into the foot pad followed by amputation at variable intervals. Our findings are (1) comparable strong therapeutic benefit resulted from treatment of mice after amputation with a GD2-KLH conjugate vaccine or with anti-GD2 monoclonal antibody 3F8. (2) The strongest correlation was between antibody induction in response to vaccination and prolonged survival. (3) Antibody titers in response to vaccination in tumor challenged mice as compared to unchallenged mice were far lower despite the absence of detectable recurrences at the time. (4) The half life of administered 3F8 monoclonal antibody (but not control antibody) in challenged mice administered was significantly shorter than the half life of 3F8 antibody in unchallenged controls. The correlation between vaccine-induced antibody titers and prolonged survival may reflect, at least in part, increased tumor burden in antibody-negative mice. Absorption of vaccine-induced antibodies by increased, although not detected tumor burden may also explain the correlation between vaccine-induced antibody titers and survival in the adjuvant clinical trials described above. © 2011 Springer-Verlag.
Keywords: controlled study; unclassified drug; overall survival; nonhuman; mouse; tumor volume; animal experiment; animal model; monoclonal antibody; liver metastasis; immunological tolerance; cancer vaccine; cancer vaccines; ganglioside gd2; tumor recurrence; lymphoma cell; antibody response; micrometastasis; amputation; tumor; antibody; immunoglobulin g antibody; monoclonal antibody 3f8; antibody titer; keyhole limpet hemocyanin; immunoglobulin m antibody; qs 21; 3f8; el4; gd2 ganglioside; gd2-klh conjugate; mab; gd2 ganglioside antibody; gd2 ganglioside keyhole limpet hemocyanin conjugate vaccine; antibody blood level; foot pad tumor
Journal Title: Cancer Immunology, Immunotherapy
Volume: 60
Issue: 5
ISSN: 0340-7004
Publisher: Springer  
Date Published: 2011-05-01
Start Page: 621
End Page: 627
Language: English
DOI: 10.1007/s00262-011-0975-9
PROVIDER: scopus
PUBMED: 21267719
PMCID: PMC3734789
DOI/URL:
Notes: --- - "Export Date: 23 June 2011" - "CODEN: CIIMD" - "Source: Scopus"
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MSK Authors
  1. Fusataka Koide
    14 Koide
  2. Nai-Kong Cheung
    447 Cheung
  3. Soo Ki Kim
    6 Kim
  4. Govindaswami Ragupathi
    133 Ragupathi
  5. Katherine S Panageas
    331 Panageas
  6. Xiaohong Wu
    6 Wu