TY - JOUR
T1 - Selection of human antitumor single-chain Fv antibodies from the B-cell repertoire of patients immunized against autologous neuroblastoma
AU - Rossig, Claudia
AU - Nuchtern, Jed G.
AU - Brenner, Malcolm
PY - 2000/12/13
Y1 - 2000/12/13
N2 - Background. We used phage display technology to clone human recombinant antitumor antibodies from the antibody repertoire of neuroblastoma patients immunized with cytokine-gene transduced tumor cells. Procedure. Lymphocytes obtained from neuroblastoma patients either at diagnosis or after immunization with an autologous interleukin-2 gene transduced tumor vaccine were used to construct two human single-chain Fv (scFV) phage libraries. Tumor-reactive phage were characterized using ELISA, flow cytometry, and sequencing analysis. Result. The initial screening after panning on neuroblastoma cells yielded a substantially higher proportion of selectivity tumor-binding phage clones derived from the immunized patients library (12.9%) than from the unvaccinated patients library (0.8%). The antibodies stained the cells from several additional pediatric malignancies, including Ewing sarcoma and rhabdomyosarcoma, in the absence of binding to any normal tissue cultures or epithelial tumor cell lines. The pattern of reactivity was different from that of antibodies recognizing other widely distributed neuroblastoma-associated antigens, suggesting recognition of a novel shared tumor antigen. Conclusion. The human recombinant scFV antibodies reported here appear to represent a tumor-specific B-cell response induce by autologous tumor immunization and are potentially useful targeting moieties for the treatment of selected childhood tumors. (C) 2000 Wiley-Liss, Inc.
AB - Background. We used phage display technology to clone human recombinant antitumor antibodies from the antibody repertoire of neuroblastoma patients immunized with cytokine-gene transduced tumor cells. Procedure. Lymphocytes obtained from neuroblastoma patients either at diagnosis or after immunization with an autologous interleukin-2 gene transduced tumor vaccine were used to construct two human single-chain Fv (scFV) phage libraries. Tumor-reactive phage were characterized using ELISA, flow cytometry, and sequencing analysis. Result. The initial screening after panning on neuroblastoma cells yielded a substantially higher proportion of selectivity tumor-binding phage clones derived from the immunized patients library (12.9%) than from the unvaccinated patients library (0.8%). The antibodies stained the cells from several additional pediatric malignancies, including Ewing sarcoma and rhabdomyosarcoma, in the absence of binding to any normal tissue cultures or epithelial tumor cell lines. The pattern of reactivity was different from that of antibodies recognizing other widely distributed neuroblastoma-associated antigens, suggesting recognition of a novel shared tumor antigen. Conclusion. The human recombinant scFV antibodies reported here appear to represent a tumor-specific B-cell response induce by autologous tumor immunization and are potentially useful targeting moieties for the treatment of selected childhood tumors. (C) 2000 Wiley-Liss, Inc.
KW - Antitumor antibody
KW - Neuroblastoma
KW - Phage display
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U2 - 10.1002/1096-911X(20001201)35:6<692::AID-MPO45>3.0.CO;2-7
DO - 10.1002/1096-911X(20001201)35:6<692::AID-MPO45>3.0.CO;2-7
M3 - Article
C2 - 11107148
AN - SCOPUS:0033659746
VL - 35
SP - 692
EP - 695
JO - Medical and Pediatric Oncology
JF - Medical and Pediatric Oncology
SN - 0098-1532
IS - 6
ER -