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Jun, Moutner, and Jaffee: Generation of Renal Cell Carcinoma-specific CD4+/CD8+ T Cells Restricted by an HLA-39 from a RCC Patient Vaccinated with GM-CSF Gene-Transduced Tumor Cells
Original Article

Immune Network 2003; 3(2): 96-102.

Published online: 30 June 2003

DOI: https://doi.org/10.4110/in.2003.3.2.96

Generation of Renal Cell Carcinoma-specific CD4+/CD8+ T Cells Restricted by an HLA-39 from a RCC Patient Vaccinated with GM-CSF Gene-Transduced Tumor Cells

Do Youn Jun1, Joseph Moutner2, Elizabeth Jaffee3

1Institute of Genetic Engineering, Kyungpook National University, Daegu 702-701, Korea.

2GSF-Institut fur Klinische Molekularbiologie, Marchioninistr. Muchen, Germany.

3Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Correspondence to: Do Youn Jun, Institute of Genetic Engineering, Kyungpook National University, Daegu 702-701, Korea. (Tel) +82 -53-950-5378, (Fax) +82-53-955-5522, dyjun@knu.ac.kr

Copyright © 2003 The Korean Association of Immunologists

(open-access):

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced tumor cell vaccines induce very potent systemic anti-tumor immunity in preclinical and clinical models. Our previous phase I clinical trial in patients with metastatic renal cell carcinoma (RCC) has demonstrated both immune cell infiltration at vaccine sites and T cell-mediated delayed-type hypersensitivity (DTH) response to whole tumor cell vaccines.

Methods

To investigate the immune responses to autologous genetically- modified tumor cell vaccines, tumor-specific CD8+ T cell lines were generated from peripheral blood lymphocytes (PBL) of a RCC patient 1.24 by repeated in vitro stimulation with either B7.1-transduced autologous RCC tumor cells or B7.1-transduced autologous tumor cells treated with interferon gamma (IFNγ), and cloned by limiting dilution.

Results

Among several RCC-specific cytotoxic T lymphocytes (CTLs), a CD4+/CD8+ double positive T cell clone (17/A2) appeared to recognize IFNγ-treated autologous RCC restricted by HLA-B39. The 17/A2 also recognized other HLA-B39 positive RCC tumor cells after IFNγ treatment.

Conclusion

These results demonstrate that autologous RCC vaccination successfully generates the tumor-specific CTL 17/A2, and suggest that the presentation and recognition of the tumor antigen by the 17/A2 might be upregulated by IFNγ.

Keywords: RCC, GM-CSF, tumor-specific cytotoxic T cells, IFNγ, cancer vaccine

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