PURPOSE: The variable regions of Ig (idiotype, Id) expressed by malignant B cells can be used as tumor-specific antigens that induce humoral and cellular immunity. However, epitopes derived from Id that stimulate human CD8(+) T-cell immunity are incompletely characterized. EXPERIMENTAL DESIGN: The clonal Ig V(L) of human myeloma cell line U266 and five primary B-cell tumors were sequenced, and peptides corresponding to the Ig V(L) region were tested for their ability to stimulate CTLs from 10 HLA-A*0201-positive normal donors. The CTLs thus generated were tested against peptide-pulsed T2 cells and autologous tumor cells. RESULTS: Fourteen peptides derived from Ig light chain (V(L)) of U266 and primary B-cell tumors were used to generate 68 CTLs lines that specifically produced IFN-γ when cocultured with peptide-pulsed T2 cells. These CTLs lysed peptide-pulsed T2 cell as well as U266 or autologous tumor targets in an HLA class I-dependent manner. Sequence analysis revealed shared V(L) T-cell epitopes in U266 and primary B-cell tumors, not previously reported within Ig heavy chain (V(H)) sequences. CONCLUSION: This study thus identifies novel immunogenic CTLs epitopes from Id V(L), suggests that they are naturally presented on the surface of B-cell malignancies, and supports their inclusion in next-generation Id vaccines. The ability to prime T cells derived from normal HLA-matched donors, rather than patients, may also have direct application to current strategies, designed to generate allogeneic tumor-specific T cells for adoptive transfer.
PURPOSE: The variable regions of Ig (idiotype, Id) expressed by malignant B cells can be used as tumor-specific antigens that induce humoral and cellular immunity. However, epitopes derived from Id that stimulate humanCD8(+) T-cell immunity are incompletely characterized. EXPERIMENTAL DESIGN: The clonal Ig V(L) of humanmyeloma cell line U266 and five primary B-cell tumors were sequenced, and peptides corresponding to the Ig V(L) region were tested for their ability to stimulate CTLs from 10 HLA-A*0201-positive normal donors. The CTLs thus generated were tested against peptide-pulsed T2 cells and autologous tumor cells. RESULTS: Fourteen peptides derived from Ig light chain (V(L)) of U266 and primary B-cell tumors were used to generate 68 CTLs lines that specifically produced IFN-γ when cocultured with peptide-pulsed T2 cells. These CTLs lysed peptide-pulsed T2 cell as well as U266 or autologous tumor targets in an HLA class I-dependent manner. Sequence analysis revealed shared V(L) T-cell epitopes in U266 and primary B-cell tumors, not previously reported within Ig heavy chain (V(H)) sequences. CONCLUSION: This study thus identifies novel immunogenic CTLs epitopes from Id V(L), suggests that they are naturally presented on the surface of B-cell malignancies, and supports their inclusion in next-generation Id vaccines. The ability to prime T cells derived from normal HLA-matched donors, rather than patients, may also have direct application to current strategies, designed to generate allogeneic tumor-specific T cells for adoptive transfer.
Authors: J Z Wimperis; M K Brenner; H G Prentice; J E Reittie; P Karayiannis; P D Griffiths; A V Hoffbrand Journal: Lancet Date: 1986-02-15 Impact factor: 79.321
Authors: David G Maloney; Arthur J Molina; Firoozeh Sahebi; Keith E Stockerl-Goldstein; Brenda M Sandmaier; William Bensinger; Barry Storer; Ute Hegenbart; George Somlo; Thomas Chauncey; Benedetto Bruno; Frederick R Appelbaum; Karl G Blume; Stephen J Forman; Peter McSweeney; Rainer Storb Journal: Blood Date: 2003-07-10 Impact factor: 22.113
Authors: Minhtran Charlotte Ngo; Jun Ando; Ann M Leen; Sravya Ennamuri; Natalia Lapteva; Juan F Vera; Amelia Min-Venditti; Martha P Mims; Helen E Heslop; Catherine M Bollard; Stephen Gottschalk; Cliona M Rooney Journal: J Immunother Date: 2014-05 Impact factor: 4.456