Targeting human B-cell malignancies through Ig light chain-specific cytotoxic T lymphocytes.

Abstract

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.

• Authors: Jinsheng Weng, Soung-Chul Cha, Satoko Matsueda, Gheath Alatrash, Michael S Popescu, Qing Yi, Jeffrey J Molldrem, Michael Wang, Sattva S Neelapu, Larry W Kwak
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 17 Issue 18 Pg. 5945-52 (Sep 15 2011) ISSN: 1557-3265 [Electronic] United States
• PMID: 21813633 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Epitopes
• Epitopes, T-Lymphocyte
• Immunoglobulin Idiotypes
• Immunoglobulin Light Chains
• Peptides

Topics

• Antigens, Neoplasm (immunology)
• Cell Line, Tumor
• Epitopes (immunology)
• Epitopes, T-Lymphocyte (immunology)
• Humans
• Immunoglobulin Idiotypes (immunology)
• Immunoglobulin Light Chains (immunology)
• Leukemia, Lymphocytic, Chronic, B-Cell (immunology)
• Multiple Myeloma (immunology)
• Peptides (immunology)
• T-Lymphocytes, Cytotoxic (immunology)
• Tissue Donors