Nature Medicine
6, 332 - 336 (2000)
doi:10.1038/73193
Regression of human metastatic renal cell carcinoma after vaccination
with tumor cell−dendritic cell hybridsAlexander Kugler1, 7, Gernot Stuhler2, 7, Peter Walden3, Gerhard Zöller1, Anke Zobywalski2, Peter Brossart2, Uwe Trefzer3, Silke Ullrich1, Claudia A. Müller4, Volker Becker5, Andreas J. Gross1, Bernhard Hemmerlein6, Lothar Kanz2, Gerhard A. Müller5
& Rolf-Hermann Ringert11
Department of Urology, University of Göttingen
, Germany
2
Department II, Medical University Clinic,
Tübingen, Germany
3
Department of Dermatology, Charité, Humboldt
University, Berlin, Germany
4
Section of Transplantation Immunology and Immunohaematology,
Department II, Medical University Clinic, Tübingen,
Germany
5
Department of Nephrology and Rheumatology, University
of Göttingen, Germany
6
Department of Pathology, University of Göttingen
, Germany
7
A.K. and G.S. contributed equally to this study.
Correspondence should be addressed to Gerhard A. Müller gmueller@med.uni-goettingen.de or Rolf-Hermann Ringert akugler@gwdg.deReports of spontaneous regressions of metastases and the demonstration
of tumor-reactive cytotoxic T lymphocytes indicate the importance of the host's
immune system in controlling the devastating course of metastatic renal cell
carcinoma1,
2,
3. Recent research indicates that immunization
with hybrids of tumor and antigen presenting cells results in protective immunity
and rejection of established tumors in various rodent models4,
5,
6,
7,
8.
Here, we present a hybrid cell vaccination study of 17 patients. Using electrofusion
techniques5, we generated hybrids of autologous tumor and allogeneic
dendritic cells that presented antigens expressed by the tumor in concert
with the co-stimulating capabilities of dendritic cells. After vaccination,
and with a mean follow-up time of 13 months, four patients completely rejected
all metastatic tumor lesions, one presented a 'mixed response',
and two had a tumor mass reduction of greater 50%. We also demonstrate induction
of HLA-A2-restricted cytotoxic T cells reactive with the Muc1 tumor-associated
antigen and recruitment of CD8+ lymphocytes into tumor challenge sites. Our
data indicate that hybrid cell vaccination is a safe and effective therapy
for renal cell carcinoma and may provide a broadly applicable strategy for
other malignancies with unknown antigens.
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