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Prepublished online as a Blood First Edition Paper on April 24, 2003; DOI 10.1182/blood-2002-08-2455.
Submitted August 12, 2002
Accepted February 4, 2003
Vaccination of cutaneous T-cell lymphoma patients using intranodal injection of autologous tumor lysate pulsed dendritic cells
Tanja Maier, Adrian Tun-Kyi, Anatoli Tassis, Karl-Peter Jungius, Guenter Burg, Reinhard Dummer, and Frank O Nestle*
Department of Dermatology, University of Zurich Hospital, Zurich, Switzerland
Institute of Diagnostic Radiology, University of Zurich Hospital, Zurich, Switzerland
* Corresponding author; email: nestle{at}derm.unizh.ch.
Cutaneous T-cell lymphoma (CTCL) is a lymphoproliferative skin disease with limited therapeutic options. Ten CTCL patients were treated with once weekly intranodal injection of 1x106 mature monocyte-derived dendritic cells (DC) pulsed with 100 µg/ml tumor lysate protein equivalent and keyhole limpet hemocyanin (50 µg/ml). Tumor specific delayed type hypersensitivity (DTH) reactions developed in 8 out of 8 patients challenged with tumor lysate pulsed DC and 3 out of 8 patients challenged with tumor lysate alone. Three out of five patients showed a significant tumor lysate specific increase of in-vitro peripheral blood lymphocyte proliferation coinciding with increased INF- production. Five out of 10 (50%) patients had an objective response. Four patients presented with a partial response (PR). Two PRs are still ongoing, the other two PRs showed a mean duration of 10.5 months. One patient demonstrated a complete response (CR) with a duration of 19 months which is currently ongoing. The remaining 5 patients presented with progressive disease. 6.8 +/- 1.4 vaccinations were necessary for the induction of an objective clinical response. Response was associated with low tumor burden. Continuation of vaccination with new tumor lysate derived from progressive lesions induced again a treatment response in 2 relapsing PR patients. Selected patients had massive infiltration of CD8+ and TIA+ cytotoxic T cells at the site of regressing lesions as well as molecular remission after therapy. Intranodal injection of autologous tumor lysate pulsed DC is well-tolerated and achieves immunological as well as objective clinical responses in selected CTCL patients.
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