ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
Targeting human B-cell malignancies through Ig light chain-specific cytotoxic T lymphocytes.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- Complementation of antigen-presenting cells to generate T lymphocytes with broad target specificity.Journal of immunotherapy (Hagerstown, Md. : 1997) · 2014Article
- Towards an off-the-shelf vaccine therapy targeting shared B-cell tumor idiotypes.American journal of blood research · 2014Review
- Successes, failures and new perspectives of idiotypic vaccination for B-cell non-Hodgkin lymphomas.Human vaccines & immunotherapeutics · 2013Review
- The promise of the anti-idiotype concept.Frontiers in oncology · 2012Article
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10 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe 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
designThe 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.
resultsFourteen 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.
conclusionThis 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.
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