In-vivo immune responses to idiotypic VH complementarity-determining region 3 peptide vaccination in B-cell non-Hodgkin's lymphoma.
Idiotypic IgM expressed by B-cell non-Hodgkin's lymphoma (NHL) is clone specific and an ideal tumour antigen for immune targeting. We previously showed that repeated rounds of in vitro stimulation of peripheral blood mononuclear cells (PBMC) with autologous idiotypic heavy variable (VH) complementarity-determining region (CDR)-3 peptide produced T-cell lines able to proliferate, produce Th1 cytokines and kill autologous target cells pulsed with the CDR3 peptide. Furthermore, fresh autologous lymphoma cells were lysed by these T-cell lines, suggesting a potential for the clinical use of the CDR3 peptide for lymphoma vaccination. In this study, we determined the specific immune responses of a patient following vaccination with VH CDR3 peptide to determine if similar immune responses observed in vitro could be elicited in vivo. The patient received three fortnightly subcutaneous injections of idiotypic CDR3 peptide. The injection sites developed inflammation after the second and third vaccinations. Peripheral blood T cells were able to proliferate and produce IFN-gamma upon rechallenge with the CDR3 peptide in vitro. Cytotoxic T lymphocytes (CTLs) for autologous CD3-depleted CDR3-pulsed PBMC were detected, but only after the first vaccination. T-cell lines generated after vaccination could lyse peptide-pulsed autologous target cells. We also detected the production of anti-CDR3 peptide antibodies in the patient's serum. We conclude that naked CDR3 peptide vaccination can result in the generation of potentially beneficial specific immune responses as predicted by in vitro studies.
Wen
Y J
YJ
Department of Haematology, University of Wales College of Medicine, Heath Park, Cardiff.
Lim
S H
SH
D000917:Antibody Formation / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D022801:Complementarity Determining Regions; D004797:Enzyme-Linked Immunosorbent Assay; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007137:Immunoglobulin alpha-Chains / Q000008:administration & dosage / Q000276:immunology*; D007159:Immunologic Tests / Q000379:methods; D007167:Immunotherapy / Q000379:methods; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012882:Skin Tests / Q000379:methods; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014612:Vaccines / Q000008:administration & dosage / Q000276:immunology*
D022801:Complementarity Determining Regions; D007137:Immunoglobulin alpha-Chains; D014612:Vaccines; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin