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Blood, 15 May 2002, Vol. 99, No. 10, pp. 3748-3755
NEOPLASIA
Vaccination with CD20 peptides induces a biologically active,
specific immune response in mice
Wendy K. Roberts,
Philip O. Livingston,
David B. Agus,
Javier Pinilla-Ibarz,
Andrew Zelenetz, and
David A. Scheinberg
From the Department of Molecular Pharmacology and
Chemistry, Weill Graduate School of Medical Sciences of Cornell
University, and the Department of Medicine, Memorial Sloan-Kettering
Cancer Center, New York, NY.
CD20 is a 33-kD B-cell antigen that is expressed from the early
pre-B-cell stage of development and is lost on differentiation of B
cells into plasma cells. Because CD20 is expressed strictly by B cells,
it is an attractive target for B-cell lymphoma therapy. Monoclonal
antibodies to CD20 have been used successfully in the treatment of
B-cell lymphomas. We hypothesized that a vaccine consisting of CD20
peptide sequences might be capable of inducing an active, specific,
humoral immune response to the protein. Vaccine therapy would have the
advantage of generating a polyclonal response to the antigen in
contrast to the monoclonal response of an infused antibody. Balb/c mice
were vaccinated with prototype vaccine constructs that consisted of
peptides representing the human or mouse CD20 extracellular sequences
conjugated to carrier proteins and mixed with QS21 adjuvant. Sera from
the vaccinated mice demonstrated high-titer, specific antibodies to
various epitopes on the immunizing peptides in enzyme-linked
immunosorbent assay, weaker antibody binding to native CD20 on cells by
flow cytometry, and antibody-mediated complement killing of
CD20+ cells in some cases. Specific proliferation and
secretion of interleukin 4 and interferon  by mouse spleen cells in
response to the immunizing peptides were also demonstrated. Mice
vaccinated with the CD20 peptide keyhole limpet hemocyanin conjugates
had a 25% decrease in CD19+ splenic B cells relative to
control mice. These data indicate that a biologically active, specific
immune response to CD20 can be elicited in mice vaccinated with CD20
peptide conjugates.
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