The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/12/1669/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 11, December 6, 1999 1669-1678

Original Article

Vaccination with Mage-3a1 Peptide–Pulsed Mature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some Metastases in Advanced Stage IV Melanoma

Beatrice Thurnera, Ina Haendlea, Claudia Rödera, Detlef Dieckmanna, Petra Keikavoussib, Helmut Jonuleitc, Armin Bendera, Christian Maczeka, Doris Schreinera, Peter von den Driescha, Eva B. Bröckerb, Ralph M. Steinmand, Alexander Enkc, Eckhart Kämpgenb, and Gerold Schulera

a Department of Dermatology, University of Erlangen-Nuremberg, D-91052 Erlangen, Germany
b Department of Dermatology, University of Würzburg, D-97080 Würzburg, Germany
c Department of Dermatology, University of Mainz, D-55131 Mainz, Germany
d Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, New York 10021
Dermatologische Klinik mit Poliklinik, Hartmannstr. 14, D-91052 Erlangen, Germany.49-9131-85-617549-9131-85-0, ext. 33661

schuler{at}derma.med.uni-erlangen.de

Dendritic cells (DCs) are considered to be promising adjuvants for inducing immunity to cancer. We used mature, monocyte-derived DCs to elicit resistance to malignant melanoma. The DCs were pulsed with Mage-3A1 tumor peptide and a recall antigen, tetanus toxoid or tuberculin. 11 far advanced stage IV melanoma patients, who were progressive despite standard chemotherapy, received five DC vaccinations at 14-d intervals. The first three vaccinations were administered into the skin, 3 x 106 DCs each subcutaneously and intradermally, followed by two intravenous injections of 6 x 106 and 12 x 106 DCs, respectively. Only minor (less than or equal to grade II) side effects were observed. Immunity to the recall antigen was boosted. Significant expansions of Mage-3A1–specific CD8+ cytotoxic T lymphocyte (CTL) precursors were induced in 8/11 patients. Curiously, these immune responses often declined after the intravenous vaccinations. Regressions of individual metastases (skin, lymph node, lung, and liver) were evident in 6/11 patients. Resolution of skin metastases in two of the patients was accompanied by erythema and CD8+ T cell infiltration, whereas nonregressing lesions lacked CD8+ T cells as well as Mage-3 mRNA expression. This study proves the principle that DC "vaccines" can frequently expand tumor-specific CTLs and elicit regressions even in advanced cancer and, in addition, provides evidence for an active CD8+ CTL–tumor cell interaction in situ as well as escape by lack of tumor antigen expression.

Key Words: dendritic cells • vaccination • active immunotherapy • melanoma • cytotoxic T lymphocytes

Abbreviations used in this paper: CNS, central nervous system; DCs, dendritic cells; DTH, delayed-type hypersensitivity; MCM, monocyte-conditioned medium; RT, reverse transcriptase; TT, tetanus toxoid.

© 1999 The Rockefeller University Press


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