Functional analysis of antigen-specific T lymphocytes by serial measurement of gene expression in peripheral blood mononuclear cells and tumor specimens.
The cloning of cancer Ags recognized by T cells has provided potentially new tools to enhance immunity against metastatic cancer. The biological monitoring of effective immunization has, however, remained a dilemma. We describe here a sensitive molecular quantitation methodology that allows analysis of in vivo immune response to vaccination. Metastatic melanoma patients were immunized with a synthetically modified peptide epitope (209-2M) from the melanoma self-Ag gp100. Using serial gene expression analysis, we report functional evidence of vaccine-induced CTL reactivity in fresh cells obtained directly from the peripheral blood of postimmunized patients. Further, we demonstrate in vivo localization of vaccine-induced immune response within the tumor microenvironment. The results of these molecular assays provide direct evidence that peptide immunization in humans can result in tumor-specific CTL that localize to metastatic sites.
Kammula
U S
US
Surgery Branch, Clinical Center, National Cancer Institute, Bethesda, MD 20892, USA.
Lee
K H
KH
Riker
A I
AI
Wang
E
E
Ohnmacht
G A
GA
Rosenberg
S A
SA
Marincola
F M
FM
D001707:Biopsy, Needle; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D019085:Fluorescent Antibody Technique, Direct; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000378:metabolism; D008545:Melanoma / Q000737:chemistry / Q000276:immunology / Q000473:pathology / Q000628:therapy; D010455:Peptides / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D012333:RNA, Messenger / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D010455:Peptides; D012333:RNA, Messenger; D007371:Interferon-gamma