Isolation and expansion of tumor-reactive cytotoxic T-cell clones for adoptive immunotherapy.
Attempts to treat patients with tumor-reactive cytotoxic T-lymphocytes (CTL) have been limited. This is due to the difficulty of isolating and expanding functionally active T-cells, which are present at extremely low frequencies in the peripheral blood. Recently developed multimers of the HLA-peptide complex mimic the natural ligand of the T-cell receptor and, therefore, fluorochrome-labeled multimers allow visualization and isolation of rare T-cells with defined specificity. Multimer-guided T-cell sorting permits the in vitro culture of antigen-specific T-cells as lines or clones. Cytolytic T-cells capable of recognizing HLA-peptide complexes endogenously processed by tumor cells are selected for further expansion, since lysis of tumor cells in vitro is a prerequisite for effective tumor elimination in vivo. The expansion of tumor-reactive CD8+ T-cells yields cell numbers sufficient for adoptive transfer. Tumor-reactive T-cells retain the functional activity in terms of cytolysis after expansion, encouraging their use in the immunotherapy of cancer patients.
Bernhard
Helga
H
Department of Hematology/Oncology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
Schmidt
Burkhard
B
Busch
Dirk H
DH
Peschel
Christian
C
D000941:Antigens / Q000276:immunology; D002021:Buffers; D002454:Cell Differentiation; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D009000:Monocytes / Q000166:cytology; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000276:immunology*
D000941:Antigens; D002021:Buffers