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Adoptive transfer of pTRP2-specific CTLs expanding by bead-based artificial antigen-presenting cells mediates anti-melanoma response.

Abstract
Cytotoxic CD8(+) T cells are key effectors in the immunotherapy of malignant and viral diseases. However, the lack of efficient methods for their in vitro priming and expansion has become a bottleneck to the development of vaccines and adoptive transfer strategies. Synthetic artificial antigen-presenting cells (aAPCs) are now emerging as an attractive tool for eliciting and expanding CTL responses. This study reported a novel approach for targeting malignant melanoma with pTRP2-specific cytotoxic T lymphocytes (CTLs) expanded from the C57BL/6 splenocytes by multiple stimulations with aAPCs made by coating H-2K(b)-Ig/pTRP2 dimeric complexes, anti-CD28 antibody, 4-1BBL molecules and CD83 molecules to cell-sized latex beads. The induced CTLs exhibited specific lysis against RMA-S cells pulsed with the peptide pTRP2 and H-2K(b+) melanoma cells expressing TRP2, while a murine Lewis lung carcinoma cell line 3LL could not be recognized by the CTLs. The peptide-specific activity was inhibited by anti-H-2K(b) monoclonal antibody Y3. Adoptive Transfer of CTLs specific for malignant melanoma expanding by the aAPCs can mediate effective anti-melanoma response. These results suggested the bead-based aAPCs coated with an MHC-Ig/peptide complex, anti-CD28 antibody, 4-1BBL and CD83 could provide a useful tool for the reproducible expansion of specific CTLs for adoptive immunotherapy.
AuthorsXiaoling Lu, Xiaobing Jiang, Ruen Liu, Hongyang Zhao, Zhihui Liang
JournalCancer letters (Cancer Lett) Vol. 271 Issue 1 Pg. 129-39 (Nov 18 2008) ISSN: 1872-7980 [Electronic] Ireland
PMID18621475 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Intramolecular Oxidoreductases
  • dopachrome isomerase
Topics
  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal (immunology)
  • Antigen-Presenting Cells (immunology)
  • Coculture Techniques
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Intramolecular Oxidoreductases (immunology)
  • Melanoma (therapy)
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes, Cytotoxic (immunology)

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