Efficient amplification of melanoma-specific CD8+ T cells using artificial antigen presenting complex.
- Author:
Jun CHANG
1
Author Information
1. College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea. tcell@ewha.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
antigen-presenting cells;
antigen presentation;
epitopes;
T-lymphocyte;
melanoma;
T-lymphocytes;
cytotoxic
- MeSH:
Substrate Specificity;
Molecular Sequence Data;
Mice, Inbred C57BL;
Mice;
Melanoma/genetics/*immunology;
Lymphocyte Count;
Genetic Vectors/genetics;
Cell Line, Tumor;
CD8-Positive T-Lymphocytes/*cytology/*immunology/metabolism;
Biomimetics/*methods;
Antigen-Presenting Cells/immunology/metabolism;
Antigen Presentation/*immunology;
Animals;
Amino Acid Sequence;
Adoptive Transfer/methods
- From:Experimental & Molecular Medicine
2006;38(6):591-598
- CountryRepublic of Korea
- Language:English
-
Abstract:
In vitro large amplification of tumor-specific cytotoxic T lymphocytes (CTLs) and adoptive transfer of these cells is one of the most promising approaches to treat malignant diseases in which an effective immune response is not achieved by active immunization. However, generating sufficient numbers of tumor-specific CTLs stimulated with autologous antigen presenting cells (APCs) in vitro is one of the most problematic steps in the adoptive cell transfer (ACT) therapy. To circumvent this problem, we have developed an artificial antigen presenting complex (aAPCs) using MHC class I molecules loaded with a melanoma-specific TRP-2 peptide epitope. Our results show that TRP-2-specific CD8+ T cells elicited by immunization with recombinant adenovirus expressing the mini-gene epitope are efficiently stimulated and amplified in vitro to a greater extent by aAPCs than by natural splenic APCs. These aAPC-induced CTLs recognized endogenously processed antigens present on B16F10 melanoma cells. Efficient stimulation and proliferation of antigen- specific T cells was also confirmed using ovalbumin peptide-loaded aAPCs and OT-I TCR transgenic cells. These results demonstrate that prior in vivo immunization, which increases the precursor frequency, simplifies posterior expansion of tumor- specific CD8+ T cells, and aAPCs is superior to autologous APC for in vitro amplification. This prime and expand regimen can be an alternative method for large amplification of rare tumor-specific CTLs and aAPCs should be a useful tool for ACT immunotherapy.
