Mimotope vaccination for epitope-specific induction of anti-CD20 antibodies.
CD20 is expressed strictly by B-cells and is ubiquitously expressed at high surface densities of malignant human B-cells. This suggests that CD20 may be a tumor target for immunotherapy of B-cell lymphomas. Rituximab, a chimeric monoclonal antibody directed against CD20, has been demonstrated to be an effective treatment for non-Hodgkin's lymphoma (NHL) and some autoimmune diseases. In the current study, we used the phage display technique to generate mimotopes that complemented the screening Ab Rituximab. A total of seven candidate mimotopes were isolated from a 12-mer peptide library from which one mimotope was conjugated to keyhole limpet hemocyanin (KLH) or tetanus toxoid (TT). The immunogenicity of the two vaccines generated was examined in BALB/c mice. Sera from the vaccinated mice demonstrated high-titer specific antibodies to the mimotope conjugates. Antibody binding to native CD20 and Ab-mediated cytotoxicity (CDC, complement-dependent cytotoxicity) were also analyzed. Our data suggest that a Rituximab mimotope may be a useful tool for the construction of a functional vaccine to treat B-cell malignancy as well as some CD20 related autoimmune disorders.
Li
Meng
M
Biotechnology Center of The Fourth Military Medical University, 17 Changle West Road, 710032 Xi'an, PR China.
Yan
Zhen
Z
Han
Wei
W
Zhang
Yingqi
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000378:metabolism; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000008:administration & dosage* / Q000276:immunology* / Q000378:metabolism; D001666:Binding Sites, Antibody; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D045744:Cell Line, Tumor; D018985:Epitopes, B-Lymphocyte / Q000008:administration & dosage* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007106:Immune Sera / Q000378:metabolism; D019169:Jurkat Cells; D016393:Lymphoma, B-Cell / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D019151:Peptide Library; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D019496:Cancer Vaccines; D018985:Epitopes, B-Lymphocyte; D007106:Immune Sera; D019151:Peptide Library; D000069283:Rituximab