Peptide-beta2-microglobulin-major histocompatibility complex expressing cells are potent antigen-presenting cells that can generate specific T cells.
Adoptive T-cell therapy represents a promising therapeutic approach for the treatment of cancer. Successful adoptive immunotherapy depends on the ex vivo priming and expansion of antigen-specific T cells. However, the in vitro generation of adequate numbers of functional antigen-specific T cell remains a major obstacle. It is important to develop efficient and reproducible methods to generate high numbers of antigen-specific T cells for adoptive T-cell transfer. We have developed a new artificial antigen-presenting cell (aAPC) by transfection of major histocompatibility (MHC) class I negative Daudi cells with a peptide-beta2-microglobulin-MHC fusion construct (single-chain aAPC) ensuring presentation of the peptide-MHC complex of interest. Using this artificial antigen-presenting cell, we could generate up to 9.2 x 10(8) antigen-specific cytotoxic CD8(+) T cells from 10 ml blood. In vitro generated T cells lysed endogenously presented antigens. Direct comparison of the single-chain aAPC with autologous monocyte-derived dendritic cells demonstrated that these cells were equally efficient in stimulation of T cells. Finally, we were able to generate antigen-specific T cell lines from perpheral blood mononuclear cells of patients receiving cytotoxic chemotherapy. The use of single-chain aAPC represent a promising option for the generation of antigen-specific CD8(+) T cells, which could be used for adoptive T-cell therapy.
Obermann
Sonja
S
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Petrykowska
Susanne
S
Manns
Michael P
MP
Korangy
Firouzeh
F
Greten
Tim F
TF
D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000032:analysis; D015789:HLA-A2 Antigen / Q000378:metabolism; D006801:Humans; D016219:Immunotherapy, Adoptive; D008113:Liver Neoplasms / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D014407:Tumor Cells, Cultured; D001613:beta 2-Microglobulin / Q000378:metabolism*
D000970:Antineoplastic Agents; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D001613:beta 2-Microglobulin