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Functional Analysis of Antigen-Specific T Lymphocytes by Serial Measurement of Gene Expression in Peripheral Blood Mononuclear Cells and Tumor Specimens

1999; American Association of Immunologists; Volume: 163; Issue: 12 Linguagem: Inglês

10.4049/jimmunol.163.12.6867

1550-6606

Udai S. Kammula, Kang-Hun Lee, Adam I. Riker, Ena Wang, Galen A. Ohnmacht, Steven A. Rosenberg, Francesco M. Marincola,

vaccines and immunoinformatics approaches

Abstract 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.