التفاصيل البيبلوغرافية
العنوان: |
Targeting human B-cell malignancies through Ig light chain specific cytotoxic T lymphocytes |
المؤلفون: |
Jinsheng Weng, Qing Yi, Gheath Alatrash, Satoko Matsueda, Sattva S. Neelapu, Jeffrey J. Molldrem, Soung Chul Cha, Michael Popescu, Larry W. Kwak, Michael Wang |
سنة النشر: |
2011 |
مصطلحات موضوعية: |
Idiotype, Cancer Research, Adoptive cell transfer, Cellular immunity, Epitopes, T-Lymphocyte, Human leukocyte antigen, Biology, Epitope, Article, Epitopes, Antigen, Immunoglobulin Idiotypes, Antigens, Neoplasm, Cell Line, Tumor, Cytotoxic T cell, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Tissue Donors, Oncology, Immunology, Cancer research, Immunoglobulin Light Chains, Multiple Myeloma, Peptides, CD8, T-Lymphocytes, Cytotoxic |
الوصف: |
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 VL of human myeloma cell line U266 and five primary B-cell tumors were sequenced, and peptides corresponding to the Ig VL 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 (VL) 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 VL T-cell epitopes in U266 and primary B-cell tumors, not previously reported within Ig heavy chain (VH) sequences. Conclusion: This study thus identifies novel immunogenic CTLs epitopes from Id VL, 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. Clin Cancer Res; 17(18); 5945–52. ©2011 AACR. |
اللغة: |
English |
URL الوصول: |
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::71330580914fcbe792b5aaf0d0cdacfb https://europepmc.org/articles/PMC3176952/ |
حقوق: |
OPEN |
رقم الأكسشن: |
edsair.doi.dedup.....71330580914fcbe792b5aaf0d0cdacfb |
قاعدة البيانات: |
OpenAIRE |