Stimulation of cytotoxic T cells against idiotype immunoglobulin of malignant lymphoma with protein-pulsed or idiotype-transduced dendritic cells.

Abstract

Because of their hypervariable regions and somatic mutations, the antigen receptor molecules of lymphomas (idiotypes) are tumor-specific antigens and attractive targets for antilymphoma immunotherapy. For the optimal induction of human idiotype-specific cytotoxic T cells (CTL), idiotype was presented to CD8(+) peripheral blood mononuclear cells by monocyte-derived autologous dendritic cells (DC) after the endocytosis of idiotype protein or by idiotype-expressing DC. Recombinant idiotype was obtained as a functionally folded Fab fragment by periplasmic expression in Escherichia coli. Idiotype-expressing DC were generated by transduction with recombinant Semliki forest virus vectors encompassing heavy- or light-chain idiotype genes. Autologous lymphoblastoid cell lines stably transfected with Epstein-Barr virus-based idiotype expression vectors were used as target cells to detect idiotype-specific lysis. CTL stimulated with idiotype-loaded DC showed strong specific, CD8-mediated, and major histocompatibility complex (MHC) class I-restricted cytotoxicity against autologous heavy- and light-chain idiotype. In contrast, stimulation with idiotype-transduced DC resulted in only moderate natural killer cell activity. These data confirm the existence of idiotype-specific CTL in patients with lymphoma, define a "good manufacturing practice"-compatible protocol for the generation of these cells without the requirement of viable lymphoma cells, and favor the processing of exogenous antigen over DC transduction for the induction of MHC I-restricted CTL against idiotypes with unknown antigenicity. (Blood. 2000;95:1342-1349)

• Authors: F Osterroth, A Garbe, P Fisch, H Veelken
• Journal: Blood (Blood) Vol. 95 Issue 4 Pg. 1342-9 (Feb 15 2000) ISSN: 0006-4971 [Print] United States
• PMID: 10666209 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Viral
• DNA Primers
• Immunoglobulin Heavy Chains
• Immunoglobulin Idiotypes
• Immunoglobulin Light Chains
• Recombinant Proteins

Topics

• Adult
• Amino Acid Sequence
• Antibodies, Viral (immunology)
• Base Sequence
• CD8-Positive T-Lymphocytes (immunology)
• Cytotoxicity, Immunologic
• DNA Primers
• Dendritic Cells (immunology)
• Female
• Humans
• Immunoglobulin Heavy Chains (genetics, immunology)
• Immunoglobulin Idiotypes (chemistry, genetics, immunology)
• Immunoglobulin Light Chains (genetics, immunology)
• Leukemia, Lymphocytic, Chronic, B-Cell (genetics, immunology, pathology)
• Lymphoma, Follicular (genetics, immunology, pathology)
• Male
• Middle Aged
• Molecular Sequence Data
• Monocytes (immunology)
• Polymerase Chain Reaction
• Recombinant Proteins (chemistry, immunology)
• Semliki forest virus (immunology)
• T-Lymphocytes, Cytotoxic (immunology)